Effects of inhalational anaesthetics in experimental allergic asthma.

PubMed

Burburan, S M; Silva, J D; Abreu, S C; Samary, C S; Guimarães, I H L; Xisto, D G; Morales, M M; Rocco, P R M

2014-06-01

We evaluated whether isoflurane, halothane and sevoflurane attenuate the inflammatory response and improve lung morphofunction in experimental asthma. Fifty-six BALB/c mice were sensitised and challenged with ovalbumin and anaesthetised with isoflurane, halothane, sevoflurane or pentobarbital sodium for one hour. Lung mechanics and histology were evaluated. Gene expression of pro-inflammatory (tumour necrosis factor-α), pro-fibrogenic (transforming growth factor-β) and pro-angiogenic (vascular endothelial growth factor) mediators, as well as oxidative process modulators, were analysed. These modulators included nuclear factor erythroid-2 related factor 2, sirtuin, catalase and glutathione peroxidase. Isoflurane, halothane and sevoflurane reduced airway resistance, static lung elastance and atelectasis when compared with pentobarbital sodium. Sevoflurane minimised bronchoconstriction and cell infiltration, and decreased tumour necrosis factor-α, transforming growth factor-β, vascular endothelial growth factor, sirtuin, catalase and glutathione peroxidase, while increasing nuclear factor erythroid-2-related factor 2 expression. Sevoflurane down-regulated inflammatory, fibrogenic and angiogenic mediators, and modulated oxidant-antioxidant imbalance, improving lung function in this model of asthma. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Alkylphenols--potential modulators of the allergic response.

PubMed

Suen, Jau-Ling; Hung, Chih-Hsin; Yu, Hsin-Su; Huang, Shau-Ku

2012-07-01

The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.

Immune responses to novel allergens and modulation of inflammation by vitamin K3 analogue: a ROS dependent mechanism.

PubMed

Kohli, Vineet; Sharma, Deepak; Sandur, Santosh Kumar; Suryavanshi, Shweta; Sainis, Krishna B

2011-02-01

The possibility of newer allergens being responsible for atopy needs to be explored at regional level due to environmental variables. Current studies were undertaken to identify common environmental allergens causing atopy in a defined population of India and to correlate the presence of various risk factors with the clinical presentation of allergy. Newer allergens like human dander and rice grain dust were identified and reported as the most common cause of atopy in this region. Atopy, elevated serum total IgE and familial tendency, was observed in 88%, 69% and 58% of allergic patients respectively. Further, allergen-specific immune responses like lymphocyte proliferation and cytokine secretion were studied in vitro using peripheral blood mononuclear cells (PBMC) isolated from both allergic and non-allergic individuals. Although, some allergens induced significant lymphocyte proliferation in vitro, allergen-induced cytokine secretion except that of TNF-α was not seen. Significantly higher ratio of secreted IL-4/IFN-γ cytokines was observed in PBMC isolated from allergic subjects in response to PHA. Plumbagin (vitamin K3 analogue) completely inhibited PHA-induced cytokine production in PBMC, in both allergic and non-allergic individuals. Plumbagin modulated the levels of intracellular reactive oxygen species and glutathione and suppressed PHA induced activation of NF-κB in human PBMC. The results thus show in human PMBC, for the first time, the anti-allergic and anti-inflammatory effects of plumbagin and underscore its therapeutic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

Airway epithelial phosphoinositide 3-kinase-δ contributes to the modulation of fungi-induced innate immune response.

PubMed

Jeong, Jae Seok; Lee, Kyung Bae; Kim, So Ri; Kim, Dong Im; Park, Hae Jin; Lee, Hern-Ku; Kim, Hyung Jin; Cho, Seong Ho; Kolliputi, Narasaiah; Kim, Soon Ha; Lee, Yong Chul

2018-04-05

Respiratory fungal exposure is known to be associated with severe allergic lung inflammation. Airway epithelium is an essential controller of allergic inflammation. An innate immune recognition receptor, nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome, and phosphoinositide 3 kinase (PI3K)-δ in airway epithelium are involved in various inflammatory processes. We investigated the role of NLRP3 inflammasome in fungi-induced allergic lung inflammation and examined the regulatory mechanism of NLRP3 inflammasome, focusing on PI3K-δ in airway epithelium. We used two in vivo models induced by exposure to Aspergillus fumigatus ( Af ) and Alternaria alternata ( Aa ), as well as an Af -exposed in vitro system. We also checked NLRP3 expression in lung tissues from patients with allergic bronchopulmonary aspergillosis (ABPA). Assembly/activation of NLRP3 inflammasome was increased in the lung of Af -exposed mice. Elevation of NLRP3 inflammasome assembly/activation was observed in Af -stimulated murine and human epithelial cells. Similarly, pulmonary expression of NLRP3 in patients with ABPA was increased. Importantly, neutralisation of NLRP3 inflammasome derived IL-1β alleviated pathophysiological features of Af -induced allergic inflammation. Furthermore, PI3K-δ blockade improved Af -induced allergic inflammation through modulation of NLRP3 inflammasome, especially in epithelial cells. This modulatory role of PI3K-δ was mediated through the regulation of mitochondrial reactive oxygen species (mtROS) generation. NLRP3 inflammasome was also implicated in Aa -induced eosinophilic allergic inflammation, which was improved by PI3K-δ blockade. These findings demonstrate that fungi-induced assembly/activation of NLRP3 inflammasome in airway epithelium may be modulated by PI3K-δ, which is mediated partly through the regulation of mtROS generation. Inhibition of PI3K-δ may have potential for treating fungi-induced severe allergic lung inflammation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models.

PubMed

Liu, Lu; Wang, Lin-Peng; He, Shan; Ma, Yan

2018-05-01

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of IgE antibodies by B cells and a decrease of the interferon-γ/interleukin-4 (Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine (CM) research on the mechanisms and effificacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the PubMed and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specifific immunoglobulin E, inflflammatory cell infifiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

Early life exposure to antibiotics and the risk of childhood allergic diseases: an update from the perspective of the hygiene hypothesis.

PubMed

Kuo, Chang-Hung; Kuo, Hsuan-Fu; Huang, Ching-Hua; Yang, San-Nan; Lee, Min-Sheng; Hung, Chih-Hsing

2013-10-01

The prevalence of allergic diseases has been growing rapidly in industrial countries during recent decades. It is postulated that growing up with less microbial exposure may render the immune system susceptible to a T helper type 2 (Th2)-predominant allergic response-also known as the hygiene hypothesis. This review delineates recent epidemiological and experimental evidence for the hygiene hypothesis, and integrates this hypothesis into the association between early life exposure to antibiotics and the development of allergic diseases and asthma. Several retrospective or prospective epidemiological studies reveal that early exposure to antibiotics may be positively associated with the development of allergic diseases and asthma. However, the conclusion is inconsistent. Experimental studies show that antibiotics may induce the Th2-skewed response by suppressing the T helper type 1 (Th1) response through inhibition of Th1 cytokines and disruption of the natural course of infection, or by disturbing the microflora of the gastrointestinal (GI) tract and therefore jeopardizing the establishment of oral tolerance and regulatory T cell immune responses. The hygiene hypothesis may not be the only explanation for the rapid increase in the prevalence of allergic diseases and asthma. Further epidemiological and experimental studies addressing the issue of the impact of environmental factors on the development of allergic diseases and the underlying mechanisms may unveil novel strategies for the prevention and treatment of allergic diseases in the future. Copyright © 2013. Published by Elsevier B.V.

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.

PubMed

Silva, F M C; Oliveira, E E; Gouveia, A C C; Brugiolo, A S S; Alves, C C; Correa, J O A; Gameiro, J; Mattes, J; Teixeira, H C; Ferreira, A P

2017-07-01

Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity. © 2017 British Society for Immunology.

Allergic rhinitis

PubMed Central

2011-01-01

Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually a long-standing condition that often goes undetected in the primary-care setting. The classic symptoms of the disorder are nasal congestion, nasal itch, rhinorrhea and sneezing. A thorough history, physical examination and allergen skin testing are important for establishing the diagnosis of allergic rhinitis. Second-generation oral antihistamines and intranasal corticosteroids are the mainstay of treatment. Allergen immunotherapy is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for allergic rhinitis is not effective or is not tolerated. This article provides an overview of the pathophysiology, diagnosis, and appropriate management of this disorder. PMID:22166009

Human Milk and Allergic Diseases: An Unsolved Puzzle

PubMed Central

Peroni, Diego G.; Boix-Amorós, Alba; Hsu, Peter S.; Van’t Land, Belinda; Skevaki, Chrysanthi; Collado, Maria Carmen; Garssen, Johan; Geddes, Donna T.; Nanan, Ralph; Slupsky, Carolyn; Wegienka, Ganesa; Kozyrskyj, Anita L.; Warner, John O.

2017-01-01

There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development. PMID:28817095

Human Milk and Allergic Diseases: An Unsolved Puzzle.

PubMed

Munblit, Daniel; Peroni, Diego G; Boix-Amorós, Alba; Hsu, Peter S; Van't Land, Belinda; Gay, Melvin C L; Kolotilina, Anastasia; Skevaki, Chrysanthi; Boyle, Robert J; Collado, Maria Carmen; Garssen, Johan; Geddes, Donna T; Nanan, Ralph; Slupsky, Carolyn; Wegienka, Ganesa; Kozyrskyj, Anita L; Warner, John O

2017-08-17

There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development.

Toxoplasma gondii Infection Suppresses House Dust Mite Extract-Induced Atopic Dermatitis in NC/Nga Mice.

PubMed

Jeong, Young Il; Hong, Sung Hee; Cho, Shin Hyeong; Lee, Won Ja; Lee, Sang Eun

2015-11-01

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects humans and animals via congenital or postnatal routes, and it is found worldwide. Modulation of the immune system by parasite infection is proposed to suppress allergic inflammation. Growing evidences have shown that interleukin (IL)-10-producing regulatory B cells (B(regs)) and CD4+CD25+FoxP3+ regulatory T cells (T(regs)) induced by parasite infection play a critical role in allergic or autoimmune diseases because these cells regulate negatively cellular immune responses and inflammation. Currently, the role of IL-10-producing regulatory B cells in host immune response during T. gondii infection is unknown. In this study, we investigate whether T. gondii infection can suppress the development of unrelated atopic dermatitis (AD)-like lesions. AD is a chronically relapsing inflammatory skin disease accompanied by severe itching; for this, we used NC/Nga mice, a well-known experimental model of systemic AD. Repeated exposure to Dermatophagoides farinae crude extract (DfE), known as a major environmental allergen, evokes AD-like skin lesions in NC/Nga mice under specific pathogen-free conditions. NC/Nga mice were intraperitoneally infected with 10 cysts of T. gondii. T. gondii infection significantly ameliorated AD-like skin lesions in NC/Nga mice. The subpopulation of B(regs) and T(regs) in the AD mice was expanded in the course of T. gondii infection. In addition, T. gondii infection inhibited Th2 and enhanced Th1 immune response in the DfE-treated AD mice. We have experimentally demonstrated for the first time that T. gondii infection ameliorated AD-like skin lesions in a mouse model of AD. Our study could in part explain the mechanisms of how parasite infection prevents the development of allergic disorder. Therefore, these immunemechanisms induced by T. gondii infection may be beneficial for the host in terms of reduced risk of allergic immune reactions.

Vitamin E Isoforms as Modulators of Lung Inflammation

PubMed Central

Abdala-Valencia, Hiam; Berdnikovs, Sergejs; Cook-Mills, Joan M.

2013-01-01

Asthma and allergic diseases are complex conditions caused by a combination of genetic and environmental factors. Clinical studies suggest a number of protective dietary factors for asthma, including vitamin E. However, studies of vitamin E in allergy commonly result in seemingly conflicting outcomes. Recent work indicates that allergic inflammation is inhibited by supplementation with the purified natural vitamin E isoform α-tocopherol but elevated by the isoform γ-tocopherol when administered at physiological tissue concentrations. In this review, we discuss opposing regulatory effects of α-tocopherol and γ-tocopherol on allergic lung inflammation in clinical trials and in animal studies. A better understanding of the differential regulation of inflammation by isoforms of vitamin E provides a basis towards the design of clinical studies and diets that would effectively modulate inflammatory pathways in lung disease. PMID:24184873

Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

PubMed

Cai, Yeping; Zhou, Jiansheng; Webb, Dianne C

2009-01-01

Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

Preventative and Therapeutic Probiotic Use in Allergic Skin Conditions: Experimental and Clinical Findings

PubMed Central

Özdemir, Öner; Göksu Erol, Azize Yasemin

2013-01-01

Probiotics are ingested live microbes that can modify intestinal microbial populations in a way that benefits the host. The interest in probiotic preventative/therapeutic potential in allergic diseases stemmed from the fact that probiotics have been shown to improve intestinal dysbiosis and permeability and to reduce inflammatory cytokines in human and murine experimental models. Enhanced presence of probiotic bacteria in the intestinal microbiota is found to correlate with protection against allergy. Therefore, many studies have been recently designed to examine the efficacy of probiotics, but the literature on the allergic skin disorders is still very scarce. Here, our objective is to summarize and evaluate the available knowledge from randomized or nonrandomized controlled trials of probiotic use in allergic skin conditions. Clinical improvement especially in IgE-sensitized eczema and experimental models such as atopic dermatitis-like lesions (trinitrochlorobenzene and picryl chloride sensitizations) and allergic contact dermatitis (dinitrofluorobenzene sensitization) has been reported. Although there is a very promising evidence to recommend the addition of probiotics into foods, probiotics do not have a proven role in the prevention or the therapy of allergic skin disorders. Thus, being aware of possible measures, such as probiotics use, to prevent/heal atopic diseases is essential for the practicing allergy specialist. PMID:24078929

Chrysin suppresses mast cell-mediated allergic inflammation: Involvement of calcium, caspase-1 and nuclear factor-{kappa}B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Yunju; Lee, Soyoung; Kim, Sang-Hyun, E-mail: shkim72@knu.ac.kr

A great number of people are suffering from allergic inflammatory diseases such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid contained in propolis, blue passion flower, and fruits. Several studies reported that chrysin has beneficial effects including anti-tumor and anti-oxidant activities. The aim of the present study was to elucidate whether chrysin modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. Chrysin inhibited immediate-type systemic hypersensitivitymore » and serum histamine release. Chrysin attenuated immunoglobulin E-mediated local anaphylaxis. These inhibitory effects of chrysin on the systemic and local allergic reaction were more potent than cromolyn, a known anti-allergic drug. Chrysin reduced histamine release from mast cells. The inhibitory effect of chrysin on the histamine release was mediated by the modulation of intracellular calcium. In addition, chrysin decreased gene expression of pro-inflammatory cytokines such as, tumor necrosis factor-{alpha}, IL (interleukin)-1{beta}, IL-4, and IL-6 in mast cells. The inhibitory effect of chrysin on the pro-inflammatory cytokine was nuclear factor-{kappa}B and caspase-1 dependent. Our findings provide evidence that chrysin inhibits mast cell-derived allergic inflammatory reactions by blocking histamine release and pro-inflammatory cytokine expression, and suggest the mechanisms of action. Furthermore, in vivo and in vitro anti-allergic inflammatory effect of chrysin suggests a possible therapeutic application of this agent in allergic inflammatory diseases. - Research Highlights: > Discovery of drugs for the allergic inflammation is important in human health. > Chrysin is a natural flavonoid contained in propolis, blue passion flower, and fruits. > Chrysin inhibited systemic and local hypersensitivity, and serum histamine release. > Chrysin decreased inflammatory cytokines through the inhibition of NF-{kappa}B and caspase-1. > Chrysin might be a candidate for the treatment of allergic inflammatory diseases.« less

Association of filaggrin variants with asthma and rhinitis: is eczema or allergic sensitization status an effect modifier?

PubMed Central

Ziyab, Ali H.; Karmaus, Wilfried; Zhang, Hongmei; Holloway, John W.; Steck, Susan E.; Ewart, Susan; Arshad, Syed Hasan

2014-01-01

Background Associations of filaggrin (FLG) variants with asthma and rhinitis have been shown to be modulated by eczema status. However, it is unknown whether allergic sensitization status modifies this association. The aim of this study was to determine whether FLG variants need eczema and/or allergic sensitization as a necessary component to execute its adverse effect on coexisting and subsequent asthma and rhinitis. Methods Repeated measurements of asthma, rhinitis, eczema, and allergic sensitization (documented by skin prick tests) at ages 1, 2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n = 1,456). FLG haploinsufficiency was defined as having at least the minor allele of R501X, 2282del4, or S3247X variants. Log binomial regression models were used to test associations and statistical interactions. Results FLG variants increased the risk of asthma (RR = 1.39, 95% CI: 1.06 – 1.80) and rhinitis (RR = 1.37, 95% CI: 1.16 – 1.63). In delayed effect models, ‘FLG variants plus allergic sensitization’ and ‘FLG variants plus eczema’ increased the risk of subsequent asthma by 4.93-fold (95% CI: 3.61 – 6.71) and 3.33-fold (95% CI: 2.45 – 4.51), respectively, during the first 18 years of life. In contrast, neither eczema nor allergic sensitization in combination with FLG variants increased the risk of later rhinitis. Conclusions Allergic sensitization and eczema modulated the association between FLG variants and asthma, but not rhinitis. Results of our study imply that the mechanisms and pathways through which FLG variants predispose to increased risk of asthma and rhinitis may be different. PMID:25277085

Disturbed sleep: linking allergic rhinitis, mood and suicidal behavior.

PubMed

Fang, Beverly J; Tonelli, Leonardo H; Soriano, Joseph J; Postolache, Teodor T

2010-01-01

Allergic inflammation is associated with mood disorders, exacerbation of depression, and suicidal behavior. Mediators of inflammation modulate sleep , with Th1 cytokines promoting NREM sleep and increasing sleepiness and Th2 cytokines (produced during allergic inflammation) impairing sleep. As sleep impairment is a rapidly modifiable suicide risk factor strongly associated with mood disorders, we review the literature leading to the hypothesis that allergic rhinitis leads to mood and anxiety disorders and an increased risk of suicide via sleep impairment. Specifically, allergic rhinitis can impair sleep through mechanical (obstructive) and molecular (cytokine production) processes. The high prevalence of mood and anxiety disorders and allergy, the nonabating suicide incidence, the currently available treatment modalities to treat sleep impairment and the need for novel therapeutic targets for mood and anxiety disorders, justify multilevel efforts to explore disturbance of sleep as a pathophysiological link.

The effects of spirulina on allergic rhinitis.

PubMed

Cingi, Cemal; Conk-Dalay, Meltem; Cakli, Hamdi; Bal, Cengiz

2008-10-01

The prevalence of allergic rhinitis is increasing globally due to various causes. It affects the quality life of a large group of people in all around the world. Allergic rhinitis still remains inadequately controlled with present medical means. The need of continuous medical therapy makes individuals anxious about the side effects of the drugs. So there is a need for an alternative strategy. Effects of spirulina, tinospora cordifolia and butterbur were investigated recently on allergic rhinitis in just very few investigations. Spirulina represents a blue-green alga that is produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. This double blind, placebo controlled study, evaluated the effectiveness and tolerability of spirulina for treating patients with allergic rhinitis. Spirulina consumption significantly improved the symptoms and physical findings compared with placebo (P < 0.001***) including nasal discharge, sneezing, nasal congestion and itching. Spirulina is clinically effective on allergic rhinitis when compared with placebo. Further studies should be performed in order to clarify the mechanism of this effect.

Association between exposure to antimicrobial household products and allergic symptoms.

PubMed

Hong, Soyoung; Kwon, Ho-Jang; Choi, Won-Jun; Lim, Wan Ryung; Kim, Jeonghoon; Kim, KyooSang

2014-01-01

Antimicrobial chemicals are used in a variety of household and personal care products. Exposure to antimicrobial household products has been hypothesized to lead to allergic diseases in children. We investigated antimicrobial household product exposure and allergic symptoms in Korean children. An antimicrobial exposure (AE) score was derived. To examine the symptoms of allergic diseases (current wheeze, current rhinitis, and current eczema) in the past 12 months, we used a questionnaire based on the core module of the International Study of Asthma and Allergies in Children. Complete data for the analysis were available for 25,805 of the 35,590 (72.5%) children. The prevalence of current allergic diseases was as follows: wheeze, 5.6%; allergic rhinitis, 32.6%; and eczema, 17.7%. The mean (standard deviation) AE score was 14.3 (9.3) (range: 0-40). Compared with subjects with a low AE score (reference), subjects with a high AE score (fourth quartile) were more likely to have symptoms of wheezing and allergic rhinitis (adjusted odds ratio [aOR] for wheezing 1.24, 95% confidence interval [CI], 1.05-1.45, p for trend=0.24; aOR for allergic rhinitis 1.30, 95% CI, 1.20-1.40, p<0.01). These findings suggest that frequent use of antimicrobial household products was associated with current wheeze and current allergic rhinitis.

RAPID COMMUNICATION IL-4 INDUCES IL-6 AND SIGNS OF ALLERGIC-TYPE INFLAMMATION IN THE NASAL AIRWAYS OF NONALLERGIC INDIVIDUALS

EPA Science Inventory

In addition to its more widely recognized role in promoting IgE synthesis, we speculate that interleukin-4 (IL-4) may modulate both allergic- and nonallergic-type inflammatory processes in the airway mucosa. We examined in vivo the effect of IL-4 on granulocyte and cytokine h...

Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis.

PubMed

Petrosino, Stefania; Verde, Roberta; Vaia, Massimo; Allarà, Marco; Iuvone, Teresa; Di Marzo, Vincenzo

2018-06-01

Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB 2 ) receptor activation was shown to reduce the production of the monocyte chemotactic protein-2 (MCP-2) chemokine in polyinosinic-polycytidylic acid [poly-(I:C)]-stimulated human keratinocyte (HaCaT) cells, an in vitro model of allergic contact dermatitis (ACD). We investigated if nonpsychotropic cannabinoids, such as cannabidiol (CBD), produced similar effects in this experimental model of ACD. HaCaT cells were stimulated with poly-(I:C), and the release of chemokines and cytokines was measured in the presence of CBD or other phytocannabinoids (such as cannabidiol acid, cannabidivarin, cannabidivarinic acid, cannabichromene, cannabigerol, cannabigerolic acid, cannabigevarin, tetrahydrocannabivarin, and tetrahydrocannabivarinic acid) and antagonists of CB 1 , CB 2 , or transient receptor potential vanilloid type-1 (TRPV1) receptors. HaCaT cell viability following phytocannabinoid treatment was also measured. The cellular levels of endocannabinoids [anandamide (AEA), 2-arachidonoylglycerol] and related molecules (palmitoylethanolamide, oleoylethanolamide) were quantified in poly-(I:C)-stimulated HaCaT cells treated with CBD. We show that in poly-(I:C)-stimulated HaCaT cells, CBD elevates the levels of AEA and dose-dependently inhibits poly-(I:C)-induced release of MCP-2, interleukin-6 (IL-6), IL-8, and tumor necrosis factor- α in a manner reversed by CB 2 and TRPV1 antagonists 6-iodopravadoline (AM630) and 5'-iodio-resiniferatoxin (I-RTX), respectively, with no cytotoxic effect. This is the first demonstration of the anti-inflammatory properties of CBD in an experimental model of ACD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

PubMed Central

Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

2013-01-01

Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

Pre-birth origins of allergy and asthma.

PubMed

Gatford, K L; Wooldridge, A L; Kind, K L; Bischof, R; Clifton, V L

2017-09-01

Allergy is a chronic disease that can develop as early as infancy, suggesting that early life factors are important in its aetiology. Variable associations between size at birth, a crude marker of the fetal environment, and allergy have been reported in humans and require comprehensive review. Associations between birth weight and allergy are however confounded in humans, and we and others have therefore begun exploring the effects of early life events on allergy in experimental models. In particular, we are using ovine models to investigate whether and how a restricted environment before birth protects against allergy, whether methyl donor availability contributes to allergic protection in IUGR, and why maternal asthma during pregnancy is associated with increased risks of allergic disease in children. We found that experimental intrauterine growth restriction (IUGR) in sheep reduced cutaneous responses to antigens in progeny, despite normal or elevated IgE responses. Furthermore, maternal methyl donor supplementation in late pregnancy partially reversed effects of experimental IUGR, consistent with the proposal that epigenetic pathways underlie some but not all effects of IUGR on allergic susceptibility. Ovine experimental allergic asthma with exacerbations reduces relative fetal size in late gestation, with some changes in immune populations in fetal thymus suggestive of increased activation. Maternal allergic asthma in mice also predisposes progeny to allergy development. In conclusion, these findings in experimental models provide direct evidence that a perturbed environment before birth alters immune system development and postnatal function, and provide opportunities to investigate underlying mechanisms and develop and evaluate interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of asthma management education program on stress and compliance of patients with allergic asthma to house dust mite.

PubMed

Yoo, Yang Sook; Cho, Ok Hee; Kim, Eun Sin; Jeong, Hye Sun

2005-06-01

This study was designed to examine the effect of asthma management education program applied to allergic asthma patients receiving immunotherapy due to house dust mite on their stress and compliance with health care regimens. A quasi experimental design with non-equivalent control group and non-synchronized design was used. The subjects of this study were 61 patients who were receiving immunotherapy at intervals of a week after their symptoms were diagnosed as house dust mite allergic asthma at the pulmonary department of a university hospital in Seoul. They were divided into an experimental group of 29 patients who received asthma management education and a control group of 32 patients. The asthma management education program was composed of group education (once) and reinforcement education (three times) with environmental therapy and immunotherapy to house dust mite. Stress significantly decreased in the experimental group compared to that in the control group. Compliance with health care regimens significantly increased in the experimental group compared to that in the control group. The results suggested that the asthma management education program is effective for the management of stress and the improvement of compliance in patients with allergic asthma to house dust mite.

Association between exposure to antimicrobial household products and allergic symptoms

PubMed Central

Hong, Soyoung; Kwon, Ho-Jang; Choi, Won-Jun; Lim, Wan Ryung; Kim, Jeonghoon; Kim, KyooSang

2014-01-01

Objectives Antimicrobial chemicals are used in a variety of household and personal care products. Exposure to antimicrobial household products has been hypothesized to lead to allergic diseases in children. Methods We investigated antimicrobial household product exposure and allergic symptoms in Korean children. An antimicrobial exposure (AE) score was derived. To examine the symptoms of allergic diseases (current wheeze, current rhinitis, and current eczema) in the past 12 months, we used a questionnaire based on the core module of the International Study of Asthma and Allergies in Children. Complete data for the analysis were available for 25,805 of the 35,590 (72.5%) children. Results The prevalence of current allergic diseases was as follows: wheeze, 5.6%; allergic rhinitis, 32.6%; and eczema, 17.7%. The mean (standard deviation) AE score was 14.3 (9.3) (range: 0-40). Compared with subjects with a low AE score (reference), subjects with a high AE score (fourth quartile) were more likely to have symptoms of wheezing and allergic rhinitis (adjusted odds ratio [aOR] for wheezing 1.24, 95% confidence interval [CI], 1.05-1.45, p for trend=0.24; aOR for allergic rhinitis 1.30, 95% CI, 1.20-1.40, p<0.01). Conclusions These findings suggest that frequent use of antimicrobial household products was associated with current wheeze and current allergic rhinitis. PMID:25420879

Immunomodulation: the future cure for allergic diseases.

PubMed

Tsitoura, Daphne C; Tassios, Yannis

2006-11-01

Allergies are the result of aberrant immune reactivity against common innocuous environmental proteins (allergens). A pivotal component of allergic pathogenesis is the generation of allergen-specific Th cells with an effector phenotype. These Th cells activate a complex immune cascade that triggers the release of potent mediators and enhances the mobilization of several inflammatory cells types, which in turn elicit the acute allergic reactions and promote the development of chronic inflammation. The current therapies for allergic diseases focus primarily on pharmacological control of symptoms and suppression of inflammation. This approach is beneficial, but not curative, since the underlying immune pathology is not inhibited. In an attempt to develop more effective therapeutic strategies, the scientific interest has been directed toward methods down-modulating the immune mechanisms that initiate and maintain the allergic cascade. Today, the only widely used disease-modifying form of allergy treatment is the specific immunotherapy with allergen extracts. More recently the use of anti-IgE has been approved for patients with allergic asthma. Other immunomodulatory methods being currently explored are the administration of microbial adjuvants that inhibit Th2 reactivity and the design of molecules that interrupt the activity of key allergic cytokines, chemokines, or other Th2 effector mediators.

Modulation of allergic immune responses by mucosal application of recombinant lactic acid bacteria producing the major birch pollen allergen Bet v 1.

PubMed

Daniel, C; Repa, A; Wild, C; Pollak, A; Pot, B; Breiteneder, H; Wiedermann, U; Mercenier, A

2006-07-01

Probiotic lactic acid bacteria (LAB) are able to modulate the host immune system and clinical trials have demonstrated that specific strains have the capacity to reduce allergic symptoms. Therefore, we aimed to evaluate the potential of recombinant LAB producing the major birch pollen allergen Bet v 1 for mucosal vaccination against birch pollen allergy. Recombinant Bet v 1-producing Lactobacillus plantarum and Lactococcus lactis strains were constructed. Their immunogenicity was compared with purified Bet v 1 by subcutaneous immunization of mice. Intranasal application of the live recombinant strains was performed to test their immunomodulatory potency in a mouse model of birch pollen allergy. Bet v 1 produced by the LAB was recognized by monoclonal anti-Bet v 1 and IgE antibodies from birch pollen-allergic patients. Systemic immunization with the recombinant strains induced significantly lower IgG1/IgG2a ratios compared with purified Bet v 1. Intranasal pretreatment led to reduced allergen-specific IgE vs enhanced IgG2a levels and reduced interleukin (IL)-5 production of splenocytes in vitro, indicating a shift towards non-allergic T-helper-1 (Th1) responses. Airway inflammation, i.e. eosinophils and IL-5 in lung lavages, was reduced using either Bet v 1-producing or control strains. Allergen-specific secretory IgA responses were enhanced in lungs and intestines after pretreatment with only the Bet v 1-producing strains. Mucosal vaccination with live recombinant LAB, leading to a shift towards non-allergic immune responses along with enhanced allergen-specific mucosal IgA levels offers a promising approach to prevent systemic and local allergic immune responses.

Eosinophil Activities Modulate the Immune/Inflammatory Character of Allergic Respiratory Responses in Mice

PubMed Central

Jacobsen, Elizabeth A.; LeSuer, William E.; Willetts, Lian; Zellner, Katie R.; Mazzolini, Kirea; Antonios, Nathalie; Beck, Brandon; Protheroe, Cheryl; Ochkur, Sergei I.; Colbert, Dana; Lacy, Paige; Moqbel, Redwan; Appleton, Judith; Lee, Nancy A.; Lee, James J.

2014-01-01

Background The importance and specific role(s) of eosinophils in modulating the immune/inflammatory phenotype of allergic pulmonary disease remain to be defined. Established animals models assessing the role(s) of eosinophils as contributors and/or causative agents of disease have relied on congenitally deficient mice where the developmental consequences of eosinophil depletion are unknown. Methods We developed a novel conditional eosinophil-deficient strain of mice (iPHIL) through a gene knock-in strategy inserting the human diphtheria toxin (DT) receptor (DTR) into the endogenous eosinophil peroxidase genomic locus. Results Expression of DTR rendered resistant mouse eosinophil progenitors sensitive to DT without affecting any other cell types. The presence of eosinophils was shown to be unnecessary during the sensitization phase of either ovalbumin (OVA) or house dust mite (HDM) acute asthma models. However, eosinophil ablation during airway challenge led to a predominantly neutrophilic phenotype (>15% neutrophils) accompanied by allergen-induced histopathologies and airway hyperresponsiveness in response to methacholine indistinguishable from eosinophilic wild type mice. Moreover, the iPHIL neutrophilic airway phenotype was shown to be a steroid-resistant allergic respiratory variant that was reversible upon restoration of peripheral eosinophils. Conclusions Eosinophil contributions to allergic immune/inflammatory responses appear to be limited to the airway challenge and not the sensitization phase of allergen provocation models. The reversible steroid-resistant character of the iPHIL neutrophilic airway variant suggests underappreciated mechanisms by which eosinophils shape the character of allergic respiratory responses. PMID:24266710

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation

PubMed Central

Mendez-Enriquez, E; Melendez, Y; Martinez, F; Baay, G; Huerta-Yepez, S; Gonzalez-Bonilla, C; Fortoul, T I; Soldevila, G; García-Zepeda, E A

2008-01-01

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides. PMID:18336592

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation.

PubMed

Mendez-Enriquez, E; Melendez, Y; Martinez, F; Baay, G; Huerta-Yepez, S; Gonzalez-Bonilla, C; Fortoul, T I; Soldevila, G; García-Zepeda, E A

2008-05-01

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides.

Emerging roles of basophils in allergic inflammation.

PubMed

Miyake, Kensuke; Karasuyama, Hajime

2017-07-01

Basophils have long been neglected in immunological studies because they were regarded as only minor relatives of mast cells. However, recent advances in analytical tools for basophils have clarified the non-redundant roles of basophils in allergic inflammation. Basophils play crucial roles in both IgE-dependent and -independent allergic inflammation, through their migration to the site of inflammation and secretion of various mediators, including cytokines, chemokines, and proteases. Basophils are known to produce large amounts of IL-4 in response to various stimuli. Basophil-derived IL-4 has recently been shown to play versatile roles in allergic inflammation by acting on various cell types, including macrophages, innate lymphoid cells, fibroblasts, and endothelial cells. Basophil-derived serine proteases are also crucial for the aggravation of allergic inflammation. Moreover, recent reports suggest the roles of basophils in modulating adaptive immune responses, particularly in the induction of Th2 differentiation and enhancement of humoral memory responses. In this review, we will discuss recent advances in understanding the roles of basophils in allergic inflammation. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Newly acquired kiwi fruit allergy after bone marrow transplantation from a kiwi-allergic donor.

PubMed

Garzorz, N; Thomas, J; Eberlein, B; Haferlach, C; Ring, J; Biedermann, T; Schmidt-Weber, C; Eyerich, K; Seifert, F; Eyerich, S

2016-07-01

The phenomenon of allergy transfer from an allergic donor to a non-allergic recipient via hematopoietic cell transplantation has been described by several reports. However, it could not yet been conclusively shown that allergic reaction of the recipient is elicited by the donor's cells. In the case of a 46-year-old male patient who - for the first time in his life - had two episodes of oral allergic syndrome upon kiwi consumption after having received myeloablative hematopoietic stem cell transplantation (HCT) from his kiwi-allergic sister, we aimed to clarify the origin of allergen reactive cells in the donor. We not only intended to demonstrate if allergy was transferred by HCT but also to present an experimental workup for the analysis of allergy transfer by HCT. Allergic sensitization to kiwi in recipient and donor was proven by ImmunoCAP. Furthermore, origin of peripheral blood mononuclear cells (PBMCs) was analyzed by chromosomal fluorescence in situ hybridization (FISH). To confirm allergic reaction and activation of hematopoietic cells by customized kiwi extract, we performed basophil activation test from whole blood as well as T cell proliferation assays from purified PBMCs of both recipient and donor. Basophil activation upon kiwi extract was demonstrated in both recipient and donor. Besides, we showed proliferation of CD4(+) T cells after incubation with kiwi extract. FISH analysis proved that hematopoietic cells of the male recipient completely originated from the female donor. Exemplified in this patient, we show for the first time that allergy transfer is mediated by the donor's cells. Moreover, our experimental approach using customized kiwi extract to prove contribution of kiwi-specific T and B cells in both kiwi-allergic recipient and donor could serve as a model approach for future studies. © 2016 European Academy of Dermatology and Venereology.

No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice

PubMed Central

Dekan, Gerhard; Epstein, Michelle M.

2014-01-01

Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma. PMID:25084284

Prevention of poison ivy and poison oak allergic contact dermatitis by quaternium-18 bentonite.

PubMed

Marks, J G; Fowler, J F; Sheretz, E F; Rietschel, R L

1995-08-01

Poison ivy and poison oak are the most common causes of allergic contact dermatitis in North America. We investigated whether a new topical lotion containing 5% quaternium-18 bentonite prevents experimentally induced poison ivy and poison oak allergic contact dermatitis. A single-blind, paired comparison, randomized, multicenter investigation was used to evaluate the effectiveness and safety of quaternium-18 bentonite lotion in preventing experimentally induced poison ivy and poison oak allergic contact dermatitis in susceptible volunteers. One hour before both forearms were patch tested with urushiol, the allergenic resin from poison ivy and poison oak, 5% quaternium-18 bentonite lotion was applied on one forearm. The test patches were removed after 4 hours and the sites interpreted for reaction 2, 5, and 8 days later. The difference in reactions between treated and untreated patch test sites was statistically analyzed. Two hundred eleven subjects with a history of allergic contact dermatitis to poison ivy and poison oak were studied. One hundred forty-four subjects had positive reactions to urushiol. The test sites pretreated with quaternium-18 bentonite lotion had absent or significantly reduced reactions to the urushiol compared with untreated control sites (p < 0.0001) on all test days. When it occurred, the reaction consistently appeared later on treated than on control sites (p < 0.0001). One occurrence of mild, transient erythema at the application site was the only side effect from the quaternium-18 bentonite lotion. Quaternium-18 bentonite lotion was effective in preventing or diminishing experimentally produced poison ivy and poison oak allergic contact dermatitis.

Human body frequency modulation by 0.9% sodium chloride solutions: a new paradigm and perspective for human health.

PubMed

Sudan, B J

2000-08-01

This case study demonstrates that the normal human body frequency, which can be disturbed by electromagnetic influences of the environment, can be modulated by 0.9% sodium chloride solutions (physiological saline) and that occurrence of allergic reactions have subsequently been suppressed as a result of this modulation. The use of distilled water as control showed no effect on occurrence of allergic reactions. Further observations on the growth of various plants in a greenhouse exposed to various geomagnetic fields support the previous observations on humans. The neutralization of electromagnetic influences on humans using 0.9% sodium chloride solution or by enclosure of plants within a copper wire Faraday cage resulting in a normal and uniform growth of plants as compared with disturbed and irregular growth in unenclosed controls, is demonstrated. These original observations propose a new strategy to suppress or prevent allergic reactions and possibly other effects observed in various human pathologies in relation to a disturbance of human body frequencies. It is hypothesized that the double helix structure of desoxyribonucleic acid (DNA) could be modified by environmental electromagnetic fields and that disresonance between the two chains of DNA could lead to the expression of specific pathology. Copyright 2000 Harcourt Publishers Ltd.

Accurate prediction of severe allergic reactions by a small set of environmental parameters (NDVI, temperature).

PubMed

Notas, George; Bariotakis, Michail; Kalogrias, Vaios; Andrianaki, Maria; Azariadis, Kalliopi; Kampouri, Errika; Theodoropoulou, Katerina; Lavrentaki, Katerina; Kastrinakis, Stelios; Kampa, Marilena; Agouridakis, Panagiotis; Pirintsos, Stergios; Castanas, Elias

2015-01-01

Severe allergic reactions of unknown etiology,necessitating a hospital visit, have an important impact in the life of affected individuals and impose a major economic burden to societies. The prediction of clinically severe allergic reactions would be of great importance, but current attempts have been limited by the lack of a well-founded applicable methodology and the wide spatiotemporal distribution of allergic reactions. The valid prediction of severe allergies (and especially those needing hospital treatment) in a region, could alert health authorities and implicated individuals to take appropriate preemptive measures. In the present report we have collecterd visits for serious allergic reactions of unknown etiology from two major hospitals in the island of Crete, for two distinct time periods (validation and test sets). We have used the Normalized Difference Vegetation Index (NDVI), a satellite-based, freely available measurement, which is an indicator of live green vegetation at a given geographic area, and a set of meteorological data to develop a model capable of describing and predicting severe allergic reaction frequency. Our analysis has retained NDVI and temperature as accurate identifiers and predictors of increased hospital severe allergic reactions visits. Our approach may contribute towards the development of satellite-based modules, for the prediction of severe allergic reactions in specific, well-defined geographical areas. It could also probably be used for the prediction of other environment related diseases and conditions.

Accurate Prediction of Severe Allergic Reactions by a Small Set of Environmental Parameters (NDVI, Temperature)

PubMed Central

Andrianaki, Maria; Azariadis, Kalliopi; Kampouri, Errika; Theodoropoulou, Katerina; Lavrentaki, Katerina; Kastrinakis, Stelios; Kampa, Marilena; Agouridakis, Panagiotis; Pirintsos, Stergios; Castanas, Elias

2015-01-01

Severe allergic reactions of unknown etiology,necessitating a hospital visit, have an important impact in the life of affected individuals and impose a major economic burden to societies. The prediction of clinically severe allergic reactions would be of great importance, but current attempts have been limited by the lack of a well-founded applicable methodology and the wide spatiotemporal distribution of allergic reactions. The valid prediction of severe allergies (and especially those needing hospital treatment) in a region, could alert health authorities and implicated individuals to take appropriate preemptive measures. In the present report we have collecterd visits for serious allergic reactions of unknown etiology from two major hospitals in the island of Crete, for two distinct time periods (validation and test sets). We have used the Normalized Difference Vegetation Index (NDVI), a satellite-based, freely available measurement, which is an indicator of live green vegetation at a given geographic area, and a set of meteorological data to develop a model capable of describing and predicting severe allergic reaction frequency. Our analysis has retained NDVI and temperature as accurate identifiers and predictors of increased hospital severe allergic reactions visits. Our approach may contribute towards the development of satellite-based modules, for the prediction of severe allergic reactions in specific, well-defined geographical areas. It could also probably be used for the prediction of other environment related diseases and conditions. PMID:25794106

Tangeretin has anti-asthmatic effects via regulating PI3K and Notch signaling and modulating Th1/Th2/Th17 cytokine balance in neonatal asthmatic mice.

PubMed

Liu, L-L; Li, F-H; Zhang, Y; Zhang, X-F; Yang, J

2017-07-20

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.

Immunologic and metabolic effects of high-refined carbohydrate-containing diet in food allergic mice.

PubMed

Yamada, Letícia Tamie Paiva; de Oliveira, Marina Chaves; Batista, Nathália Vieira; Fonseca, Roberta Cristelli; Pereira, Rafaela Vaz Sousa; Perez, Denise Alves; Teixeira, Mauro Martins; Cara, Denise Carmona; Ferreira, Adaliene Versiani Matos

2016-02-01

Allergic mice show a reduction in body weight and adiposity with a higher inflammatory response in the adipose tissue similar to obese fat tissue. This study aimed to evaluate whether the low-grade inflammatory milieu of mice with diet-induced mild obesity interferes with the allergic response induced by ovalbumin (OVA). BALB/c mice were divided into four groups: 1) non-allergic (OVA-) mice fed chow diet, 2) allergic (OVA+) mice fed chow diet, 3) OVA- mice fed high-refined carbohydrate-containing (HC) diet, and 4) OVA+ mice fed HC diet. After 5 wk, allergic groups were sensitized with OVA and received a booster 14 d later. All groups received an oral OVA challenge 7 d after the booster. Allergic groups showed increased serum levels of total IgE, anti-OVA IgE, and IgG1; a high disease activity index score; aversion to OVA; and increased intestinal eosinophil infiltration. Non-allergic mild-obese mice also showed aversion to OVA and an increased number of eosinophils in the proximal jejunum. After the allergic challenge, OVA+ mice fed chow diet showed weight loss and lower adiposity in several adipose tissue depots. OVA+ mice fed HC diet showed a loss of fat mass only in the mesenteric adipose tissue. Furthermore, increased levels of TNF, IL-6, and IL-10 were observed in this tissue. Our data show that mild-obese allergic mice do not present severe pathologic features of food allergy similar to those exhibited by lean allergic mice. Mild obesity promoted by HC diet ingestion causes important intestinal disorders that appear to modulate the inflammatory response during the antigen challenge. Copyright © 2016 Elsevier Inc. All rights reserved.

Antigen-Specific Induction of Osteopontin Contributes to the Chronification of Allergic Contact Dermatitis

PubMed Central

Seier, Anne M.; Renkl, Andreas C.; Schulz, Guido; Uebele, Tanja; Sindrilaru, Anca; Iben, Sebastian; Liaw, Lucy; Kon, Shigeyuki; Uede, Toshimitsu; Weiss, Johannes M.

2010-01-01

Allergic contact dermatitis is a T cell-mediated immune response, which in its relapsing chronic form is of high socioeconomic impact. The phosphoglycoprotein osteopontin (OPN) has chemotactic and Th1 cytokine functions and in various models is essential for robust T cell-mediated immunity. Here we demonstrate that OPN is abundantly expressed by both effector T cells and keratinocytes in allergic contact dermatitis lesions. T cells from nickel-allergic donors secrete high levels of OPN following antigen-specific stimulation. OPN may substitute for missing IFN-γ secretion in T effector cells because low IFN-γ-producing T cell clones secrete high levels of OPN, and OPN down-modulates their interleukin-4 expression. Furthermore, interferon-γ from T effector cells augments OPN in allergic contact dermatitis by inducing OPN in keratinocytes, which in turn polarizes dendritic cells and attracts inflammatory cells. In the murine contact hypersensitivity (CHS) model for allergic contact dermatitis, OPN is strongly induced in antigen-specific proliferating T cells, and OPN null mice display a reduced chronic CHS inflammatory response due to a decreased influx of effector T cells. Importantly, because of its function for chronic allergic contact dermatitis, OPN may well be a therapeutic target, because anti-OPN antibody treatment in part suppresses established chronic CHS. PMID:20008129

SUPPRESSION OF ALLERGIC UVEITIS BY 6-MERCAPTOPURINE

PubMed Central

Wirostko, E.; Halbert, S. P.

1962-01-01

Experimental uveitis in rabbits was induced by single intraocular antigen injection. Treatment with 6-MP for 14 days suppressed the allergic inflammation and antibody response. A good correlation was demonstrated between the degree of uveitis and the antibody titer. PMID:14001284

HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.

PubMed

Osbourn, Megan; Soares, Dinesh C; Vacca, Francesco; Cohen, E Suzanne; Scott, Ian C; Gregory, William F; Smyth, Danielle J; Toivakka, Matilda; Kemter, Andrea M; le Bihan, Thierry; Wear, Martin; Hoving, Dennis; Filbey, Kara J; Hewitson, James P; Henderson, Holly; Gonzàlez-Cìscar, Andrea; Errington, Claire; Vermeren, Sonja; Astier, Anne L; Wallace, William A; Schwarze, Jürgen; Ivens, Alasdair C; Maizels, Rick M; McSorley, Henry J

2017-10-17

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses. Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Early gut colonization by Bifidobacterium breve and B. catenulatum differentially modulates eczema risk in children at high risk of developing allergic disease.

PubMed

Ismail, Intan H; Boyle, Robert J; Licciardi, Paul V; Oppedisano, Frances; Lahtinen, Sampo; Robins-Browne, Roy M; Tang, Mimi L K

2016-12-01

An altered compositional signature and reduced diversity of early gut microbiota are linked to development of allergic disease. We investigated the relationship between dominant Bifidobacterium species during the early post-natal period and subsequent development of allergic disease in the first year of life. Faecal samples were collected at age 1 week, 1 month and 3 months from 117 infants at high risk of allergic disease. Bifidobacterium species were analysed by quantitative PCR and terminal restriction fragment length polymorphism. Infants were examined at 3, 6 and 12 months, and skin prick test was performed at 12 months. Eczema was diagnosed according to the UK Working Party criteria. The presence of B. catenulatum at 3 months was associated with a higher risk of developing eczema (OR adj = 4.5; 95% CI: 1.56-13.05, p adj = 0.005). Infants colonized with B. breve at 1 week (OR adj = 0.29; 95% CI: 0.09-0.95, p adj = 0.04) and 3 months (OR adj = 0.15; 95% CI: 0.05-0.44, p adj = 0.00001) had a reduced risk of developing eczema. Furthermore, the presence of B. breve at 3 months was associated with a lower risk of atopic sensitization at 12 months (OR adj = 0.38; 95% CI: 0.15-0.98, p adj = 0.05). B. breve colonization patterns were influenced by maternal allergic status, household pets and number of siblings. Temporal variations in Bifidobacterium colonization patterns early in life are associated with later development of eczema and/or atopic sensitization in infants at high risk of allergic disease. Modulation of the early microbiota may provide a means to prevent eczema in high-risk infants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Worming Their Way into the Picture: Microbiota Help Helminths Modulate Host Immunity.

PubMed

Reynolds, Lisa A; Finlay, B Brett

2015-11-17

Parasitic helminths are potent regulators of host immunity, including inhibition of allergic inflammation. In this issue of Immunity, Zaiss et al. (2015) reveal that microbiota compositional shifts during helminth infection contribute to the multifaceted ways that helminths modulate host immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

PubMed Central

LIM, YUNSOOK; VASU, VIHAS T.; VALACCHI, GIUSEPPE; LEONARD, SCOTT; AUNG, HNIN HNIN; SCHOCK, BETTINA C.; KENYON, NICHOLAS J.; LI, CHIN-SHANG; TRABER, MARET G.; CROSS, CARROLL E.

2009-01-01

Allergic asthma is a complex immunologically mediated disease associated with increased oxidative stress and altered antioxidant defenses. It was hypothesized that α-tocopherol (α-T) decreases oxidative stress and therefore its absence may influence allergic inflammatory process, a pathobiology known to be accompanied by oxidative stress. Therefore, selected parameters of allergic asthma sensitization and inflammation were evaluated following ovalbumin sensitization and re-challenge of α-T transfer protein (TTP) knock-out mice (TTP–/–) that have greatly reduced lung α-T levels (e.g. < 5%) compared to their litter mate controls (TTP+/+). Results showed that severe α-T deficiency result in a blunted lung expression of IL-5 mRNA and IL-5 protein and plasma IgE levels compared with TTP+/+ mice following immune sensitization and rechallenge, although lung lavage eosinophil levels were comparable in both genomic strains. It is concluded that the initial stimulation of immune responses by the TTP–/– mice were generally blunted compared to the TTP+/+ mice, thus diminishing some aspects of subsequent allergic inflammatory processes. PMID:18404538

Pidotimod exacerbates allergic pulmonary infection in an OVA mouse model of asthma.

PubMed

Fu, Luo-Qin; Li, Ya-Li; Fu, Ai-Kun; Wu, Yan-Ping; Wang, Yuan-Yuan; Hu, Sheng-Lan; Li, Wei-Fen

2017-10-01

Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control). The authors determined that treatment with pidotimod exacerbated pulmonary inflammation as demonstrated by significantly increased eosinophil infiltration, dramatically elevated immunoglobulin E production, and enhanced T helper 2 response. Moreover, treatment failed to attenuate mucus production in lung tissue, and did not reduce OVA‑induced high levels of FIZZ1 and Arg1 expression in asthmatic mice. In contrast, administration of dexamethasone was efficient in alleviating allergic airway inflammation in OVA‑induced asthmatic mice. These data indicated that pidotimod as an immunotherapeutic agent should be used cautiously and the effectiveness for controlling allergic asthma needs further evaluation and research.

Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation.

PubMed

Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S; Pucillo, Carlo E

2011-10-01

Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca(++) influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.

Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation

PubMed Central

Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S.; Pucillo, Carlo E.

2011-01-01

Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease. PMID:21653238

Acinetobacter baumannii Infection Inhibits Airway Eosinophilia and Lung Pathology in a Mouse Model of Allergic Asthma

PubMed Central

Qiu, Hongyu; KuoLee, Rhonda; Harris, Greg; Zhou, Hongyan; Miller, Harvey; Patel, Girishchandra B.; Chen, Wangxue

2011-01-01

Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen. PMID:21789200

EFFECTS OF PARTICLES FROM TWO GERMAN CITIES ON ALLERGIC RESPONSES IN MICE

EPA Science Inventory

EFFECTS OF PARTICLES FROM TWO GERMAN CITIES ON ALLERGIC RESPONSES IN MICE. S. H. Gavett, L. R. Bishop, N. Haykal-Coates, J. Heinrich*, and M. I. Gilmour. Experimental Toxicology Division, ORD/NHEERL, U.S. EPA, Research Triangle Park, NC, USA, *GSF, Neuherberg, Germany.
Chi...

Histomorphometric study of the periodontal ligament in the initial period of orthodontic movement in Wistar rats with induced allergic asthma.

PubMed

Machado, Cristiane Correia Pereira; Nojima, Matilde da Cunha Gonçalves; Rodrigues e Silva, Patrícia Machado; Mandarim-de-Lacerda, Carlos Alberto

2012-09-01

Asthma is a common systemic disease occurring in infancy and adolescence, time periods that could encompass orthodontic treatment. Asthma is an inflammatory disease; therefore, it might interfere with orthodontic tooth movement. The purpose of the study was to analyze the histomorphologic aspects of the periodontal ligament of asthmatic Wistar rats in the initial period of orthodontic movement. Thirty-two Wistar rats were divided into 4 groups: 2 control groups consisting of rats without induced allergic asthma, and 2 experimental groups consisting of rats with induced allergic asthma. The animals of the first control and experimental groups did not receive orthodontic forces, whereas those in the second control and experimental groups were subjected to mesial movement of the maxillary left first molar for 3 days. The samples were prepared for histomorphometric analysis of the periodontal ligament. The area of the periodontal ligament was calculated as a function of root length in the cervical and apical regions of the distal face of the maxillary first molar mesial root. The Student t test and the Welch correlation test were applied to the data obtained. There was a statistically significant difference (P <0.05) between the control and experimental groups. An enhanced response to orthodontic force was observed in the asthmatic animals: the periodontal ligament was more compressed at the pressure area and more stretched in the traction area. Our findings indicate that experimental allergic asthma seems to exacerbate orthodontic movement in rats. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Effects of allergic diseases and age on the composition of serum IgG glycome in children

PubMed Central

Pezer, Marija; Stambuk, Jerko; Perica, Marija; Razdorov, Genadij; Banic, Ivana; Vuckovic, Frano; Gospic, Adrijana Miletic; Ugrina, Ivo; Vecenaj, Ana; Bakovic, Maja Pucic; Lokas, Sandra Bulat; Zivkovic, Jelena; Plavec, Davor; Devereux, Graham; Turkalj, Mirjana; Lauc, Gordan

2016-01-01

It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients’ IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children’s Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children. PMID:27616597

Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma.

PubMed

Skuljec, Jelena; Chmielewski, Markus; Happle, Christine; Habener, Anika; Busse, Mandy; Abken, Hinrich; Hansen, Gesine

2017-01-01

Cellular therapy with chimeric antigen receptor (CAR)-redirected cytotoxic T cells has shown impressive efficacy in the treatment of hematologic malignancies. We explored a regulatory T cell (Treg)-based therapy in the treatment of allergic airway inflammation, a model for asthma, which is characterized by an airway hyper-reactivity (AHR) and a chronic, T helper-2 (Th2) cell-dominated immune response to allergen. To restore the immune balance in the lung, we redirected Tregs by a CAR toward lung epithelia in mice upon experimentally induced allergic asthma, closely mimicking the clinical situation. Adoptively transferred CAR Tregs accumulated in the lung and in tracheobronchial lymph nodes, reduced AHR and diminished eosinophilic airway inflammation, indicated by lower cell numbers in the bronchoalveolar lavage fluid and decreased cell infiltrates in the lung. CAR Treg cells furthermore prevented excessive pulmonary mucus production as well as increase in allergen-specific IgE and Th2 cytokine levels in exposed animals. CAR Tregs were more efficient in controlling asthma than non-modified Tregs, indicating the pivotal role of specific Treg cell activation in the affected organ. Data demonstrate that lung targeting CAR Treg cells ameliorate key features of experimental airway inflammation, paving the way for cell therapy of severe allergic asthma.

Limonene and its ozone-initiated reaction products attenuate allergic lung inflammation in mice.

PubMed

Hansen, Jitka S; Nørgaard, Asger W; Koponen, Ismo K; Sørli, Jorid B; Paidi, Maya D; Hansen, Søren W K; Clausen, Per Axel; Nielsen, Gunnar D; Wolkoff, Peder; Larsen, Søren Thor

2016-11-01

Inhalation of indoor air pollutants may cause airway irritation and inflammation and is suspected to worsen allergic reactions. Inflammation may be due to mucosal damage, upper (sensory) and lower (pulmonary) airway irritation due to activation of the trigeminal and vagal nerves, respectively, and to neurogenic inflammation. The terpene, d-limonene, is used as a fragrance in numerous consumer products. When limonene reacts with the pulmonary irritant ozone, a complex mixture of gas and particle phase products is formed, which causes sensory irritation. This study investigated whether limonene, ozone or the reaction mixture can exacerbate allergic lung inflammation and whether airway irritation is enhanced in allergic BALB/cJ mice. Naïve and allergic (ovalbumin sensitized) mice were exposed via inhalation for three consecutive days to clean air, ozone, limonene or an ozone-limonene reaction mixture. Sensory and pulmonary irritation was investigated in addition to ovalbumin-specific antibodies, inflammatory cells, total protein and surfactant protein D in bronchoalveolar lavage fluid and hemeoxygenase-1 and cytokines in lung tissue. Overall, airway allergy was not exacerbated by any of the exposures. In contrast, it was found that limonene and the ozone-limonene reaction mixture reduced allergic inflammation possibly due to antioxidant properties. Ozone induced sensory irritation in both naïve and allergic mice. However, allergic but not naïve mice were protected from pulmonary irritation induced by ozone. This study showed that irritation responses might be modulated by airway allergy. However, aggravation of allergic symptoms was observed by neither exposure to ozone nor exposure to ozone-initiated limonene reaction products. In contrast, anti-inflammatory properties of the tested limonene-containing pollutants might attenuate airway allergy.

Eosinophils in Autoimmune Diseases

PubMed Central

Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

2017-01-01

Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

Probiotic treatment during neonatal age provides optimal protection against experimental asthma through the modulation of microbiota and T cells.

PubMed

Nunes, Caroline Fraga; Nogueira, Jeane S; Vianna, Pedro Henrique Oliveira; Ciambarella, Bianca Torres; Rodrigues, Patrícia Machado; Miranda, Karla Rodrigues; Lobo, Leandro Araújo; Domingues, Regina Maria Cavalcanti Pillotto; Busch, Mileane; Atella, Georgia Correa; Vale, André Macedo; Bellio, Maria; Nóbrega, Alberto; Canto, Fábio B; Fucs, Rita

2018-04-03

The incidence of allergic diseases, which increased to epidemic proportions in developed countries over the last few decades, has been correlated with altered gut microbiota colonization. Although probiotics may play a critical role in the restoration of gut homeostasis, their efficiency in the control of allergy is controversial. Here, we aimed to investigate the effects of probiotic treatment initiated at neonatal or adult ages on the suppression of experimental ovalbumin (OVA)-induced asthma. Neonatal or adult mice were orally treated with probiotic bacteria and subjected to OVA-induced allergy. Asthma-like symptoms, microbiota composition and frequencies of the total CD4+ T lymphocytes and CD4+Foxp3+ regulatory T (Treg) cells were evaluated in both groups. Probiotic administration to neonates, but not to adults, was necessary and sufficient for the absolute prevention of experimental allergen-induced sensitization. The neonatally acquired tolerance, transferrable to probiotic-untreated adult recipients by splenic cells from tolerant donors, was associated with modulation of gut bacterial composition, augmented levels of cecum butyrate and selective accumulation of Treg cells in the airways. Our findings reveal that a cross-talk between a healthy microbiota and qualitative features inherent to neonatal T cells, especially in the Treg cell subset, might support the beneficial effect of perinatal exposure to probiotic bacteria on the development of long-term tolerance to allergens.

Allergic responses and aryl hydrocarbon receptor novel pathway of mast cell activation.

PubMed

Sibilano, Riccardo; Pucillo, Carlo E; Gri, Giorgia

2015-01-01

The activation of the transcription factor aryl hydrocarbon receptor (AhR) is modulated by a wide variety of xenobiotics and ligands deriving from products of metabolism. The study of the contribution of AhR to allergic diseases has gained much interest in recent years. Here we discuss the role that environmental factors and metabolic products, particularly acting on AhR-expressing mast cells (MCs), could have in the development of local allergic/atopic response. Thus, this review will cover: a brief overview of the AhR mechanism of action in the immune system; a description of different AhR ligands and their effects to IgE-mediated MC activation in the allergic response, with particular attention to the role of IL-17; a discussion about the potential involvement of AhR in immune tolerance; and a conclusion on human diseases in which direct AhR activation of MC might have a major impact. Copyright © 2014 Elsevier Ltd. All rights reserved.

Experimental allergic encephalitis in animals, and its bearing upon the etiology of neuroparalytic accidents following antirabies treatment in man

PubMed Central

Jervis, George A.

1954-01-01

In an attempt to throw light upon the etiology of neuroparalytic accidents following antirabies treatment in man, the author analyses the process and effects of experimentally induced allergic encephalitis in various animals. He concludes that the two conditions are apparently identical, and suggests that the solution to the problem of neuroparalytic complications be sought in either the elimination of the encephalitogenic factor or the use of an antirabies vaccine which does not contain brain tissue. PMID:13182606

Effect of acupuncture on house dust mite specific IgE, substance P, and symptoms in persistent allergic rhinitis.

PubMed

McDonald, John Leslie; Smith, Peter K; Smith, Caroline A; Changli Xue, Charlie; Golianu, Brenda; Cripps, Allan W

2016-06-01

Clinical evidence suggests that acupuncture improves symptoms in persistent allergic rhinitis, but the physiologic basis of these improvements is not well understood. A randomized, sham-controlled trial of acupuncture for persistent allergic rhinitis in adults investigated possible modulation of mucosal immune responses. A total of 151 individuals were randomized into real and sham acupuncture groups (who received twice-weekly treatments for 8 weeks) and a no acupuncture group. Various cytokines, neurotrophins, proinflammatory neuropeptides, and immunoglobulins were measured in saliva or plasma from baseline to 4-week follow-up. Statistically significant reduction in allergen specific IgE for house dust mite was seen only in the real acupuncture group, from 18.87 kU/L (95% CI, 10.16-27.58 kU/L) to 17.82 kU/L (95% CI, 9.81-25.83 kU/L) (P = .04). A mean (SE) statistically significant down-regulation was also seen in proinflammatory neuropeptide substance P (SP) 18 to 24 hours after the first treatment from 408.74 (299.12) pg/mL to 90.77 (22.54) pg/mL (P = .04). No significant changes were seen in the other neuropeptides, neurotrophins, or cytokines tested. Nasal obstruction, nasal itch, sneezing, runny nose, eye itch, and unrefreshed sleep improved significantly in the real acupuncture group (postnasal drip and sinus pain did not) and continued to improve up to 4-week follow-up. Acupuncture modulated mucosal immune response in the upper airway in adults with persistent allergic rhinitis. This modulation appears to be associated with down-regulation of allergen specific IgE for house dust mite, which this study is the first to report. Improvements in nasal itch, eye itch, and sneezing after acupuncture are suggestive of down-regulation of transient receptor potential vanilloid 1. Australian New Zealand Clinical Trials Registry Identifier: ACTRN 12610001052022. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Allergic sensitization enhances anion current responsiveness of murine trachea to PAR-2 activation.

PubMed

Rievaj, Juraj; Davidson, Courtney; Nadeem, Ahmed; Hollenberg, Morley; Duszyk, Marek; Vliagoftis, Harissios

2012-03-01

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention. Here, we studied immediate changes in transepithelial short circuit current (I (sc)) induced by PAR-2 activation in the tracheas of naive and allergic mice. Activation of PAR-2 with an apically added activation peptide (AP) induced a small increase in I (sc), while a much larger increase was observed following basolateral AP addition. In ovalbumin-sensitized and -challenged animals used as a model of allergic airway inflammation, the effect of basolateral AP addition was enhanced. Responses to basolateral AP in both naive and allergic mice were not decreased by blocking sodium absorption with amiloride or CFTR function with CFTR(inh)172 but were reduced by the cyclooxygenase inhibitor indomethacin and largely blocked (>80%) by niflumic acid, a calcium-activated chloride channels' (CaCC) blocker. Allergic mice also showed an enhanced response to ATP and thapsigargin. There was no change in mRNA expression of Par-2 or of the chloride channels Ano1 (Tmem16a) and Bestrophin 2 in tracheas from allergic mice, while mRNA levels of Bestrophin 1 were increased. In conclusion, basolateral PAR-2 activation in the mouse airways led to increased anion secretion through apical CaCC, which was more pronounced in allergic animals. This could be a protective mechanism aimed at clearing allergens and defending against mucus plugging.

Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung

2014-02-01

A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited themore » expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.« less

T Cells

MedlinePlus

... cells — have proven successful in treating animals with experimental allergic encephalomyelitis (EAE), an animal model of MS. Pilot clinical trials are in progress. Future experimental therapies may involve antibodies directed against the cytokines ...

Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination

PubMed Central

Pedotti, Rosetta; DeVoss, Jason J.; Youssef, Sawsan; Mitchell, Dennis; Wedemeyer, Jochen; Madanat, Rami; Garren, Hideki; Fontoura, Paulo; Tsai, Mindy; Galli, Stephen J.; Sobel, Raymond A.; Steinman, Lawrence

2003-01-01

Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc ɛ receptor 1 (FcɛRI), and tryptase. We now demonstrate that, in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), mediated by T helper 1 (Th1) T cells, histamine receptor 1 and 2 (H1R and H2R) are present on inflammatory cells in brain lesions. Th1 cells reactive to myelin proteolipid protein expressed more H1R and less H2R than Th2 cells. Pyrilamine, an H1R antagonist, blocked EAE, and the platelet activating factor receptor antagonist CV6209 reduced the severity of EAE. EAE severity was also decreased in mice with disruption of the genes encoding Ig FcγRIII or both FcγRIII and FcɛRI. Prostaglandin D synthase and tryptase transcripts were elevated in EAE brain. Taken together, these data reveal extensive involvement of elements of the immune response associated with allergy in autoimmune demyelination. The pathogenesis of demyelination must now be viewed as encompassing elements of both Th1 responses and “allergic” responses. PMID:12576552

Clostridium difficile colonization and/or infection during infancy and the risk of childhood allergic diseases.

PubMed

Lee, Sun Hwa; Gong, Yun Na; Ryoo, Eell

2017-05-01

The gut microbiota can influence several diseases through immune modulation; however, the exact role of microbes such as Clostridium difficile and the relationship between microbiota colonization and allergic diseases are not well known. This study aimed to determine the relationship between C. difficile colonization and/or infection (CDCI) during infancy and allergic diseases during early childhood. Infants 1-12 months of age presenting changes in bowel habits for more than 2 weeks were enrolled in this study. After dividing them into 2 groups according to the presence and absence of C. difficile , the risk of allergic disease development during childhood was identified and compared. Sixty-five patients were included in this study; 22 (33.8%) were diagnosed with CDCI. No significant differences were observed in baseline characteristics between the C. difficile -positive and -negative groups except for antibiotic exposure (22.7% vs. 60.5%, P =0.004). Compared to the C. difficile -negative group, the risk of developing at least one allergic disease was higher in the C. difficile -positive group after adjusting other variables (adjusted odds ratios, 5.61; 95% confidence interval, 1.52-20.74; P =0.007). Furthermore, food allergies were more prevalent in the C. difficile -positive group ( P =0.03). CDCI during infancy were associated with a higher risk of developing allergic diseases during early childhood. These results suggest that CDCI during infancy might reflect the reduced diversity of the intestinal microbiota, which is associated with an increased risk of allergic sensitization. To identify the underlying mechanism, further investigation and a larger cohort study will be needed.

Lipid Rafts in Mast Cell Biology

PubMed Central

Silveira e Souza, Adriana Maria Mariano; Mazucato, Vivian Marino; Jamur, Maria Célia; Oliver, Constance

2011-01-01

Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization. PMID:21490812

Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model.

PubMed

Thomas, Debra J; Husmann, Robert J; Villamar, Mauricio; Winship, Timothy R; Buck, Rachael H; Zuckermann, Federico A

2011-02-28

Probiotics have been studied as immunomodulatory agents of allergy. Several human probiotic trials tracking the development of eczema and other forms of allergy have yielded inconsistent results. A recent infant study demonstrated that pre and postnatal Lactobacillus rhamnosus HN001 (HN001) supplementation decreased the prevalence of eczema and IgE associated eczema. However, the influence of HN001 on the incidence of wheeze, asthma, and/or other allergic manifestations has yet to be reported. This study was conducted to determine the effects of the probiotic HN001 on the development of allergic lung disease in a pig model. Allergy was induced by a series of subcutaneous and intratracheal sensitizations with Ascaris suum allergen (ASA) during a six week time frame in post-weanling pigs supplemented daily with HN001, or without supplementation. One week following final sensitization intradermal skin tests and respiratory challenges were conducted. In response to intradermal and respiratory challenges, ASA-sensitized pigs fed HN001 had less severe skin flare reactions, smaller increases in pleural pressure, and trends towards lower changes in arterial oxygen and carbon dioxide partial pressure levels compared to control pigs. The frequency of ASA-specific IFN-γ-secreting peripheral blood mononuclear cells, as well as the amount of IL-10 produced by ASA-specific cells, was of greater magnitude in probiotic-fed pigs compared to control animals. These observations suggest that differences in clinical responses to the allergen challenges may be related to probiotic-induced modulation of Th1 (IFN-γ) and regulatory (IL-10) cytokine expression. Probiotic supplementation decreased the severity of allergic skin and lung responses in allergen-sensitized pigs with a corresponding increase in IFN-γ expression. A similar correlation between certain allergic responses and increased IFN-γ expression has been reported in human clinical studies of allergy; this pig model of allergy may be indicative of potential probiotic modulation of allergic lung disease in humans.

Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

PubMed

Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

2015-11-15

Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Epigenetics mediate environment : gene effects on occupational sensitization.

PubMed

Pacheco, Karin A

2012-04-01

Epigenetics is the study of stable modifications of fixed genomes that direct which genes are expressed and which are silenced. Epigenetic changes are modulated by environmental exposures, making epigenetics the interface between genes and environment. This has particular relevance in understanding the effect of occupational exposures on the expression of allergic disease. The goal of this review is to describe how epigenetic changes affect transcription potential, and to examine more closely the effect of specific environmental and occupational exposures on epigenetic variations that alter allergy gene transcripts and the inflammatory milieu. Gene transcription is activated when specific CpG sites are demethylated and histones are acetylated, and, conversely, silenced when sites are methylated and histones deacetylated. The development of Th1 and Th2 phenotypes, and expression of Treg cells, are now known to be modulated by epigenetic mechanisms. Workplace exposures such as tobacco smoke, particulates, diesel exhaust, polyaromatic hydrocarbons, ozone, and endotoxin, among others, suppress Treg development, and enhance expression of inflammatory cytokines and allergic phenotypes by epigenetic means. Epigenetic manipulation to open and close transcription sites provides flexibility of gene expression in response to changing environmental cues. It may also be the window whereby allergic disease in the workplace can be reduced by targeted environmental interventions.

The mycotoxin deoxynivalenol facilitates allergic sensitization to whey in mice.

PubMed

Bol-Schoenmakers, M; Braber, S; Akbari, P; de Graaff, P; van Roest, M; Kruijssen, L; Smit, J J; van Esch, B C A M; Jeurink, P V; Garssen, J; Fink-Gremmels, J; Pieters, R H H

2016-11-01

Intestinal epithelial stress or damage may contribute to allergic sensitization against certain food antigens. Hence, the present study investigated whether impairment of intestinal barrier integrity by the mycotoxin deoxynivalenol (DON) contributes to the development of whey-induced food allergy in a murine model. C3H/HeOuJ mice, orally exposed to DON plus whey once a week for 5 consecutive weeks, showed whey-specific IgG1 and IgE in serum and an acute allergic skin response upon intradermal whey challenge, although early initiating mechanisms of sensitization in the intestine appeared to be different compared with the widely used mucosal adjuvant cholera toxin (CT). Notably, DON exposure modulated tight-junction mRNA and protein levels, and caused an early increase in IL-33, whereas CT exposure affected intestinal γδ T cells. On the other hand, both DON- and CT-sensitized mice induced a time-dependent increase in the soluble IL-33 receptor ST2 (IL-1R1) in serum, and enhanced local innate lymphoid cells type 2 cell numbers. Together, these results demonstrate that DON facilitates allergic sensitization to food proteins and that development of sensitization can be induced by different molecular mechanisms and local immune responses. Our data illustrate the possible contribution of food contaminants in allergic sensitization in humans.

Iron Supplementation Decreases Severity of Allergic Inflammation in Murine Lung

PubMed Central

Hale, Laura P.; Kant, Erin Potts; Greer, Paula K.; Foster, W. Michael

2012-01-01

The incidence and severity of allergic asthma have increased over the last century, particularly in the United States and other developed countries. This time frame was characterized by marked environmental changes, including enhanced hygiene, decreased pathogen exposure, increased exposure to inhaled pollutants, and changes in diet. Although iron is well-known to participate in critical biologic processes such as oxygen transport, energy generation, and host defense, iron deficiency remains common in the United States and world-wide. The purpose of these studies was to determine how dietary iron supplementation affected the severity of allergic inflammation in the lungs, using a classic model of IgE-mediated allergy in mice. Results showed that mice fed an iron-supplemented diet had markedly decreased allergen-induced airway hyperreactivity, eosinophil infiltration, and production of pro-inflammatory cytokines, compared with control mice on an unsupplemented diet that generated mild iron deficiency but not anemia. In vitro, iron supplementation decreased mast cell granule content, IgE-triggered degranulation, and production of pro-inflammatory cytokines post-degranulation. Taken together, these studies show that iron supplementation can decrease the severity of allergic inflammation in the lung, potentially via multiple mechanisms that affect mast cell activity. Further studies are indicated to determine the potential of iron supplementation to modulate the clinical severity of allergic diseases in humans. PMID:23029172

Absence of Foxp3+ Regulatory T Cells during Allergen Provocation Does Not Exacerbate Murine Allergic Airway Inflammation

PubMed Central

Baru, Abdul Mannan; Ganesh, Venkateswaran; Krishnaswamy, Jayendra Kumar; Hesse, Christina; Untucht, Christopher; Glage, Silke; Behrens, Georg; Mayer, Christian Thomas; Puttur, Franz; Sparwasser, Tim

2012-01-01

Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naïve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC)-transgenic Foxp3-DTR (DEREG) mice we demonstrate that the absence of Foxp3+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3+ Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics. PMID:23071726

Modulation of allergy risk by breast feeding.

PubMed

Heinrich, Joachim

2017-05-01

Breastfeeding has been suggested as a candidate for primary prevention of allergies. However, recent comprehensive and thoughtfully written systematic reviews reported mixed results and that overall there is only little evidence for breastfeeding being protective against allergic disorders. As these reviews last searched for relevant studies on 2 October 2014, the aim of our review is to shed light on the association between breastfeeding and allergic disorders (asthma, eczema, allergic rhinitis) recently published. These recent studies are varied and differ in size, settings, design, depth of data collecting, and quality of the study. Thus far, the results on the association between nonexclusive and exclusive breastfeeding with regards to asthma are mixed especially in young ages. Additionally, if eczema and allergic rhinitis are the outcomes of interest, this recent review does not provide a clearer picture. The current guidelines by WHO and European Academy of Allergy and Clinical Immunology (EAACI) on breastfeeding till 6 months and exclusively breastfeeding for 4-6 months, respectively, for the prevention of allergies are not supported by the recent study results. Nevertheless, breastfeeding should be strongly recommended for other beneficial health effects than allergy prevention.

SENSITIZATION AND EXACERBATION OF ALLERGIC DISEASES BY DIESEL ENGINE PARTICLES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Diaz-Sanchez, David

2000-08-20

Most studies of the health effects of diesel exhaust have focused on the controversial issue of its role in cancer. However, recently the role of combustion products such as diesel exhaust particles (DEP) in modulating the immune response has garnered much attention. In particular the effect of DEP on allergic and asthmatic diseases has been the focus of many studies. A link between industrialization and allergic disease has long been presumed. Indeed, only 50 years after the first recorded reported case of allergy in 1819, Charles Blackely wrote that the ''hay-fever epidemic'' was associated with the movement of people frommore » the country into the cities. Ishizaki et al. (1987) found that people in Japan living on busy roads lined with cedar trees have more allergies to cedar than residents living on similar streets with much less traffic. Since that time other epidemiological studies have reported similar findings. Kramer, et al., showed that hay fever is greater in residential areas with heavy truck traffic, while Weiland, et al., reported that allergic symptoms correlate with the distance of residences to roads with heavy traffic.« less

Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

PubMed

de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

2017-06-24

Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10 5 human AD-MSCs, or EVs (released by 10 5  AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3 + CD4 + T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3 + CD4 + T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3 + CD4 + T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different mechanisms of action of AD-MSCs versus their EVs.

Developments in the field of allergy in 2009 through the eyes of Clinical and Experimental Allergy.

PubMed

Chu, H W; Lloyd, C M; Karmaus, W; Maestrelli, P; Mason, P; Salcedo, G; Thaikoottathil, J; Wardlaw, A J

2010-11-01

In 2009 the journal published in the region of 200 papers including reviews, editorials, opinion pieces and original papers that ran the full gamut of allergic disease. It is instructive to take stock of this output to determine patterns of interest and where the cutting edge lies. We have surveyed the field of allergic disease as seen through the pages of Clinical and Experimental Allergy (CEA) highlighting trends, emphasizing notable observations and placing discoveries in the context of other key papers published during the year. The review is divided into similar sections as the journal. In the field of Asthma and Rhinitis CEA has contributed significantly to the debate about asthma phenotypes and expressed opinions about the cause of intrinsic asthma. It has also added its halfpennyworth to the hunt for meaningful biomarkers. In Mechanisms the considerable interest in T cell subsets including Th17 and T regulatory cells continues apace and the discipline of Epidemiology continues to invoke a steady stream of papers on risk factors for asthma with investigators still trying to explain the post-second world war epidemic of allergic disease. Experimental Models continue to make important contributions to our understanding of pathogenesis of allergic disease and in the Clinical Allergy section various angles on immunotherapy are explored. New allergens continue to be described in the allergens section to make those allergen chips even more complicated. A rich and vibrant year helpfully summarized by some of our associate editors. © 2010 Blackwell Publishing Ltd.

Developments in the field of allergy in 2009 through the eyes of Clinical and Experimental Allergy

PubMed Central

Chu, H. W.; Lloyd, C. M.; Karmaus, W.; Maestrelli, P.; Mason, P.; Salcedo, G.; Thaikoottathil, J.; Wardlaw, A. J.

2012-01-01

Summary In 2009 the journal published in the region of 200 papers including reviews, editorials, opinion pieces and original papers that ran the full gamut of allergic disease. It is instructive to take stock of this output to determine patterns of interest and where the cutting edge lies. We have surveyed the field of allergic disease as seen through the pages of Clinical and Experimental Allergy (CEA) highlighting trends, emphasizing notable observations and placing discoveries in the context of other key papers published during the year. The review is divided into similar sections as the journal. In the field of Asthma and Rhinitis CEA has contributed significantly to the debate about asthma phenotypes and expressed opinions about the cause of intrinsic asthma. It has also added its halfpennyworth to the hunt for meaningful biomarkers. In Mechanisms the considerable interest in T cell subsets including Th17 and T regulatory cells continues apace and the discipline of Epidemiology continues to invoke a steady stream of papers on risk factors for asthma with investigators still trying to explain the post-second world war epidemic of allergic disease. Experimental Models continue to make important contributions to our understanding of pathogenesis of allergic disease and in the Clinical Allergy section various angles on immunotherapy are explored. New allergens continue to be described in the allergens section to make those allergen chips even more complicated. A rich and vibrant year helpfully summarized by some of our associate editors. PMID:21039970

Gene expression of subunits of the IL-12 family cytokines in moDCs derived in vitro from the cord blood of children of healthy and allergic mothers.

PubMed

Hrdý, J; Novotná, O; Kocourková, I; Prokešová, L

2014-01-01

The incidence of allergic diseases is steadily increasing an urgent need to clarify the immunologic processes which occur early in life and signal an increased risk of possible future allergy development. The ratio and maturation state of DCs together with the cytokine environment are important in directing and modulating immune responses. The maturation state (presence of CD83) of cord blood monocyte-derived dendritic cells (moDCs) of 52 children of healthy mothers and 58 children of allergic mothers was estimated by flow cytometry. The capacity of moDCs to express genes for subunits of IL-12 family cytokines was monitored using real-time PCR and protein secretion in cell culture supernatants by ELISA. The percentage of CD83+ moDCs was significantly higher in the allergic group after LPS stimulation (43.11 ± 4.41) in comparison to the healthy group (24.85 ± 3.37). Significantly higher gene expression of subunits of IL-12 family members was observed in moDCs of children of allergic mothers, in comparison with children of healthy mothers. The differences were evident mainly after LPS stimulation of moDCs (healthy group: p19: 3.05 ± 1.24; p28: 14.8 ± 6.8; p35: 1.8 ± 0.6; p40: 8.0 ± 3.5; EBI3: 3.0 ± 1.2; allergic group: p19: 6.1 ± 2.7; p28: 61.4 ± 22.2; p35: 14.9 ± 6.5; p40: 36.4 ± 18.8; EBI3: 11.3 ± 3.2), with the exception of p28, whose expression was significantly higher in the allergic group even without stimulation (healthy group: 0.28 ± 0.12, allergic group: 0.87 ± 0.62). No significant difference between the healthy and allergic groups was found at the protein level. The observation of both increased presence of cell surface activation marker on moDCs and higher IL-12 family gene expression in LPS-stimulated moDCs of children of allergic mothers indicates a higher reactivity of these cells.

Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.

PubMed

Racke, M K; Bonomo, A; Scott, D E; Cannella, B; Levine, A; Raine, C S; Shevach, E M; Röcken, M

1994-11-01

The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.

The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

PubMed Central

Zaiss, Mario M.; Rapin, Alexis; Lebon, Luc; Dubey, Lalit Kumar; Mosconi, Ilaria; Sarter, Kerstin; Piersigilli, Alessandra; Menin, Laure; Walker, Alan W.; Rougemont, Jacques; Paerewijck, Oonagh; Geldhof, Peter; McCoy, Kathleen D.; Macpherson, Andrew J.; Croese, John; Giacomin, Paul R.; Loukas, Alex; Junt, Tobias; Marsland, Benjamin J.; Harris, Nicola L.

2015-01-01

Summary Intestinal helminths are potent regulators of their host’s immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions. PMID:26522986

Randomized controlled trial of fish oil supplementation in pregnancy on childhood allergies.

PubMed

Palmer, D J; Sullivan, T; Gold, M S; Prescott, S L; Heddle, R; Gibson, R A; Makrides, M

2013-11-01

Diets high in n-3 long chain polyunsaturated fatty acids (LCPUFA) may modulate the development of IgE-mediated allergic disease and have been proposed as a possible allergy prevention strategy. The aim of this study was to determine whether n-3 LCPUFA supplementation of pregnant women reduces IgE-mediated allergic disease in their children. Follow-up of children (n = 706) at hereditary risk of allergic disease in the Docosahexaenoic Acid to Optimise Mother Infant Outcome randomized controlled trial. The intervention group (n = 368) was randomly allocated to receive fish oil capsules (providing 900 mg of n-3 LCPUFA daily) from 21 weeks' gestation until birth; the control group (n = 338) received matched vegetable oil capsules without n-3 LCPUFA. The diagnosis of allergic disease was made during medical assessments at 1 and 3 years of age. No differences were seen in the overall percentage of children with IgE-mediated allergic disease in the first 3 years of life between the n-3 LCPUFA and control groups (64/368 (17.3%) vs 76/338 (22.6%); adjusted relative risk 0.78; 95% CI 0.58-1.06; P = 0.11). Eczema was the most common allergic disease; 13.8% of children in the n-3 LCPUFA group had eczema with sensitization compared with 19.0% in the control group (adjusted relative risk 0.75; 95% CI 0.53-1.05; P = 0.10). Overall, n-3 LCPUFA supplementation during pregnancy did not significantly reduce IgE-associated allergic disease in the first 3 years of life. Further studies should examine whether the nonsignificant reductions in IgE-associated allergies are of clinical and public health significance. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

PubMed

Hwang, C-J; Park, M-H; Jung, H-W; Park, Y-K; Kim, Y-H; Kang, J-S; Cho, C-W

2013-11-01

Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis. © Georg Thieme Verlag KG Stuttgart · New York.

Allergies and Disease Severity in Childhood Narcolepsy: Preliminary Findings.

PubMed

Aydinoz, Secil; Huang, Yu-Shu; Gozal, David; Inocente, Clara O; Franco, Patricia; Kheirandish-Gozal, Leila

2015-12-01

Narcolepsy frequently begins in childhood, and is characterized by excessive daytime sleepiness, with the presence of cataplexy reflecting a more severe phenotype. Narcolepsy may result from genetic predisposition involving deregulation of immune pathways, particularly involving T helper 2 cells (Th2). Increased activation of Th2 cells is usually manifested as allergic conditions such as rhinitis, atopic dermatitis, and asthma. We hypothesized that the presence of allergic conditions indicative of increased Th2 balance may dampen the severity of the phenotype in children with narcolepsy. A retrospective chart review of childhood narcolepsy patients was conducted at three major pediatric sleep centers. Patients were divided into those with narcolepsy without cataplexy (NC-) and narcolepsy with cataplexy (NC+). Demographics, polysomnographic and multiple sleep latency test data, and extraction of information on the presence of allergic diseases such allergic rhinitis, atopic dermatitis, and asthma was performed. There were 468 children identified, with 193 children in NC- group and 275 patients in the NC+ group. Overall, NC+ children were significantly younger, had higher body mass index, and had shorter mean sleep latencies and increased sleep onset rapid eye movement events. The frequency of allergic conditions, particularly asthma and allergic rhinitis, was markedly lower in NC+ (58/275) compared to NC- patients (94/193; P < 0.0001). Involvement of the immune system plays an important role in the pathophysiology of narcolepsy. Current findings further suggest that an increased shift toward T helper 2 cells, as indicated by the presence of allergic conditions, may modulate the severity of the phenotype in childhood narcolepsy, and reduce the prevalence of cataplexy in these patients. © 2015 Associated Professional Sleep Societies, LLC.

The relationship between bifidobacteria and allergic asthma and/or allergic dermatitis: a prospective study of 0-3 years-old children in Turkey.

PubMed

Akay, Hatice Kubra; Bahar Tokman, Hrisi; Hatipoglu, Nevin; Hatipoglu, Huseyin; Siraneci, Rengin; Demirci, Mehmet; Borsa, Baris Ata; Yuksel, Pelin; Karakullukcu, Asiye; Kangaba, Achille Aime; Sirekbasan, Serhat; Aka, Sibel; Mamal Torun, Muzeyyen; Kocazeybek, Bekir S

2014-08-01

Bifidobacteria are beneficial bacteria for humans. These bacteria are particularly effective at protecting against infectious diseases and modulating the immune response. It was shown that in newborns, the fecal distribution of the colonizing Bifidobacterium species influences the prevalence of allergic diseases. This study aimed to compare the faecal Bifidobacterium species of allergic children to those of healthy children to detect species level differences in faecal distribution. Stool samples were obtained from 99 children between 0 and 3 years of age whose clinical symptoms and laboratory reports were compatible with atopic dermatitis and allergic asthma. Samples were also obtained from 102 healthy children who were similar to the case group with respect to age and sex. Bifidobacteria were isolated by culture and identified at the genus level by API 20 A. In addition, 7 unique species-specific primers were used for the molecular characterization of bifidobacteria. The McNemar test was used for statistical analyses, and p < 0.05 was accepted as significant. Bifidobacterium longum was detected in 11 (11.1%) of the allergic children and in 31 (30.3%) of the healthy children. Statistical analysis revealed a significant difference in the prevalence of B. longum between these two groups (X(2): 11.2, p < 0.001). However, no significant differences in the prevalence of other Bifidobacterium species were found between faecal samples from healthy and allergic children. (p > 0.05). The significant difference in the isolation of B. longum from our study groups suggests that this species favors the host by preventing the development of asthma and allergic dermatitis. Based on these results, we propose that the production of probiotics in accordance with country-specific Bifidobacterium species densities would improve public health. Thus, country-specific prospective case-control studies that collect broad data sets are needed. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of a probiotic Escherichia coli strain on regulatory T-cells in six year-old children.

PubMed

Hrdý, J; Kocourková, I; Lodinová-Žádníková, R; Kolářová, L; Prokešová, L

2016-11-30

Probiotics are believed to prevent or reduce allergy development but the mechanism of their beneficial effect is still poorly understood. Immune characteristics of regulatory T cells (Tregs) in peripheral blood of perinatally probiotic-supplemented children of allergic mothers (51 children), non-supplemented children of allergic mothers (42 children), and non-supplemented children of healthy mothers (28 children) were compared at the age of 6-7 years. A first dose of a probiotic Escherichia coli strain (E. coli O83:K24:H31) was administered within 2 days after the birth and then 12 times during the first months of life and children were followed longitudinally. Proportion and functional properties of Tregs were estimated by flow cytometry in relation to the children's allergy status. Proportion of Tregs in the peripheral blood of children suffering from allergy tends to be higher whereas median of fluorescence intensity (MFI) of FoxP3 was significantly decreased in allergic group. Intracellular presence of regulatory cytokine interleukin (IL)-10 was also lower in allergic children. Immune functions of Tregs reflected by both MFI of FoxP3 and IL-10 in the group of probiotic-supplemented children of allergic mothers were nearly comparable with children of healthy mothers while probiotic non-supplemented children of allergic mothers have decreased immune function of Tregs. Supplementation by probiotic E. coli strain decreases allergy incidence in high-risk children. In contrast to our expectation, proportion of Tregs has not been increased in probiotic supplemented children. Beneficial effect of probiotics on newborn immature immune system could be, at least partially, explained by the modulating immune function of Tregs. In summary, we detected increased proportion of Tregs in peripheral blood of allergic children, their functional properties were decreased in comparison with the Tregs of healthy children. A unifying hypothesis for these findings is that Treg numbers in allergic children are increased in order to compensate for decreased function.

Multi-modal antigen specific therapy for autoimmunity.

PubMed

Legge, K L; Bell, J J; Li, L; Gregg, R; Caprio, J C; Zaghouani, H

2001-10-01

Peripheral tolerance, represents an attractive strategy to down-regulate previously activated T cells and suppress an ongoing disease. Herein, immunoglobulins (Igs) were used to deliver self and altered self peptides for efficient peptide presentation without costimulation to test for modulation of experimental allergic encephalomyelitis (EAE). Accordingly, the encephalitogenic proteolipid protein (PLP) sequence 139-151 (referred to as PLP1) and an altered form of PLP1 known as PLP-LR were genetically expressed on Igs and the resulting Ig-PLP1 and Ig-PLP-LR were tested for efficient presentation of the peptides and for amelioration of ongoing EAE. Evidence is presented indicating that Ig-PLP1 as well as Ig-PLP-LR given in saline to mice with ongoing clinical EAE suppresses subsequent relapses. However, aggregation of both chimeras allows crosslinking of Fcgamma receptors (FcgammaRs) and induction of IL-10 production by APCs but does not promote the up-regulation of costimulatory molecules. Consequently, IL-10 displays bystander suppression and synergizes with presentation without costimulation to drive effective modulation of EAE. As Ig-PLP1 is more potent than Ig-PLP-LR in the down-regulation of T cells, we conclude that peptide affinity plays a critical role in this multi-modal approach of T cell modulation.

Investigating the Awareness and Knowledge of Secondary School Students about the Effects of Allergic Pollen on Human Health: A Case of Burdur Province

ERIC Educational Resources Information Center

Tuzlak, Kadir

2016-01-01

The overall objective of this study is to increase the awareness of secondary school students of the effects of pollen allergy on human health by mapping allergic pollens appearing in Burdur atmosphere. This study is a pre-test and post-test experimental design. Mix method is applied thus. Both qualitative and quantitative data are gathered. The…

In vivo Expression of Inducible Nitric Oxide Synthase in Experimentally Induced Neurologic Diseases

NASA Astrophysics Data System (ADS)

Koprowski, Hilary; Zheng, Yong Mu; Heber-Katz, Ellen; Fraser, Nigel; Rorke, Lucy; Fu, Zhen Fang; Hanlon, Cathleen; Dietzschold, Bernhard

1993-04-01

The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

[Improvement of the knowledge on allergic cross-reactions between two drug groups: beta-lactams and NSAIDS].

PubMed

Sánchez-Quiles, I; Nájera-Pérez, M D; Calleja-Hernández, M Á; Martinez-Martínez, F; Belchí-Hernández, J; Canteras, M

2013-01-01

To identify opportunities for improving the available knowledge of health care professionals (particularly, physicians, pharmacists, and nurses) on crossed allergic reactions (CAR) to penicillins and NSAIDs. Quasi-experimental prospective pre-exposure study at a 412-beds hospital. An assessment of the knowledge on CAR to penicillins and NSAIDs was performed by means of anonymous questionnaires before (1st questionnaire) and after (2d questionnaire) the implementation of a series of improvement measures: protocol of "patient allergic to drugs", pocket card, poster with summarized information, and informative talks. The questionnaires served as the CRF and the statistical analysis was done with the SPSS v18.0 software. The mean number of errors in the first questionnaire on CARs of penicillin allergic patient and on CARs of NSAIDs allergic patients was 20.53 and 27.62, respectively. The mean number of errors in the second questionnaire on CARs of penicillin allergic patient and on CARs of NSAIDs allergic patients was 2.27 and 7.26, respectively. All the results were significant for a p level < 0.005. - There is insufficient knowledge on CARs to penicillins and NSAIDS, which justifies improvement measures. - After the implementation of improvement measures, there is an increased knowledge on CARs to penicillins and NSAIDs in the study groups. Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.

Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils.

PubMed

Vega, Antonio; Chacón, Pedro; Alba, Gonzalo; El Bekay, Rajaa; Martín-Nieto, José; Sobrino, Francisco

2006-07-01

Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up-regulation of its COX-2 isoform is responsible for the increased PG release, taking place under inflammatory conditions, and also, is thought to be involved in allergic and inflammatory diseases. In the present work, we demonstrate that COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies and by antigens in human neutrophils from allergic patients. This induction was detected at mRNA and protein levels and was accompanied by a concomitant PGE(2) and thromboxane A(2) release. We also show evidence that inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2-aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone, completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting that this process is mediated by reactive oxygen species (ROS) derived from NADPH oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-regulated kinase, and also, the transcription factor, nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2 expression, as specific chemical inhibitors of these two kinases, such as SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2 induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2 expression through MAPK and NF-kappaB pathways. Present results underscore a new role for ROS as second messengers in the modulation of COX-2 expression by human neutrophils in allergic conditions.

Comparative immunology of allergic responses.

PubMed

Gershwin, Laurel J

2015-01-01

Allergic responses occur in humans, rodents, non-human primates, avian species, and all of the domestic animals. These responses are mediated by immunoglobulin E (IgE) antibodies that bind to mast cells and cause release/synthesis of potent mediators. Clinical syndromes include naturally occurring asthma in humans and cats; atopic dermatitis in humans, dogs, horses, and several other species; food allergies; and anaphylactic shock. Experimental induction of asthma in mice, rats, monkeys, sheep, and cats has helped to reveal mechanisms of pathogenesis of asthma in humans. All of these species share the ability to develop a rapid and often fatal response to systemic administration of an allergen--anaphylactic shock. Genetic predisposition to development of allergic disease (atopy) has been demonstrated in humans, dogs, and horses. Application of mouse models of IgE-mediated allergic asthma has provided evidence for a role of air pollutants (ozone, diesel exhaust, environmental tobacco smoke) in enhanced sensitization to allergens.

Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

PubMed

Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

2014-12-01

Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity. © ISFM and AAFP 2014.

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses

PubMed Central

Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-01-01

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma. PMID:28775364

dNP2-ctCTLA-4 inhibits German cockroach extract-induced allergic airway inflammation and hyper-responsiveness via inhibition of Th2 responses.

PubMed

Lim, Sangho; Ho Sohn, Jung; Koo, Ja-Hyun; Park, Jung-Won; Choi, Je-Min

2017-08-04

German cockroaches are major household allergens that can trigger allergic airway inflammatory diseases with sensitive T-cell responses. Although the use of immune modulatory biologics, such as antibodies, to mediate allergic responses has recently been examined, only systemic administration is available because of the size limitations on intranasal administration. Here we utilized a cell-permeable peptide, dNP2, to deliver the cytoplasmic domain of cytotoxic T-lymphocyte antigen-4 (ctCTLA-4) through the airway epithelium to modulate Th2 responses in a German cockroach extract (GCE)-induced allergic airway inflammation model. The intranasal delivery efficiency of the dNP2-dTomato protein to the lungs was higher in GCE-induced asthmatic lung parenchymal cells compared to the sham cells. Intranasal administration of the dNP2-ctCTLA-4 protein inhibited airway hyper-responsiveness and reduced airway inflammation and remodeling, including goblet cell metaplasia and collagen deposition around the bronchi. The number of infiltrated cells, including eosinophils, and the levels of IL-4, IL-5, IL-13 and IFN-γ in the lungs were significantly reduced, presumably owing to inhibition of Th2 differentiation. However, intranasal administration of CTLA4-Ig did not inhibit airway inflammation. These results collectively suggest that dNP2-ctCTLA-4 is an efficient intranasally applicable candidate biologic for treating allergic asthma.

Modulation of the immune response by infection with Cryptosporidium spp. in children with allergic diseases.

PubMed

Guangorena-Gómez, J O; Maravilla-Domínguez, A; García-Arenas, G; Cervantes-Flores, M; Meza-Velázquez, R; Rivera-Guillén, M; Acosta-Saavedra, L C; Goytia-Acevedo, R C

2016-08-01

It has been demonstrated that the allergic response can be ameliorated by the administration of pathogen derivatives that activate Toll-like receptors and induce a Th1-type immune response (IR). Cryptosporidium is a parasite that promotes an IR via Toll-like receptors and elicits the production of Th1-type cytokines, which limit cryptosporidiosis. The aim of this study was to investigate allergy-related immune markers in children naturally infected with Cryptosporidium. In a cross-sectional study, 49 children with or without clinical diagnosis of allergies, oocysts of Cryptosporidium spp. in the faeces were screened microscopically. We microscopically screened for leucocytes, examined T and B cells for allergy-related activation markers using flow cytometry and evaluated serum for total IgE using chemiluminescence. Children with allergies and Cryptosporidium in the faeces had significantly lower levels of total IgE, B cells, CD19(+) CD23(+) and CD19(+) CD124(+) cells as well as a greater percentage of interferon-gamma (IFN-γ(+) ) and IL-4(+) CD4(+) cells than children with allergies without Cryptosporidium. This is the first description of the modulation of the IR in children with allergic diseases in the setting of natural Cryptosporidium infection. Our findings suggest the involvement of CD4(+) cells producing IL-4 and IFN-γ in the IR to Cryptosporidium in naturally infected children. © 2016 John Wiley & Sons Ltd.

Mycobacterium bovis BCG mycobacteria--new application.

PubMed

Kowalewicz-Kulbat, Magdalena; Pestel, Joël; Biet, Franck; Locht, Camille; Tonnel, André-Bernard; Druszczyńska, Magdalena; Rudnicka, Wiesława

2006-01-01

The polarized response of T helper-2 (Th2) lymphocytes to an allergen is considered to be the main cause of the pathogenesis of asthma. In this study, we asked a question whether M. bovis BCG mycobacteria which are known for the preferential stimulation of T helper-1 (Th1) immunity, diminish the effector functions of Th2 cells from allergic patients upon stimulation with a common house dust mite Der p-1 allergen. Our results allow a positive answer to this question. We demonstrate that BCG modulates the dendritic cell-dependent allergen presentation process and switches naive T lymphocytes towards an anti-allergic Th1 profile.

Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo.

PubMed

Gilles-Stein, S; Beck, I; Chaker, A; Bas, M; McIntyre, M; Cifuentes, L; Petersen, A; Gutermuth, J; Schmidt-Weber, C; Behrendt, H; Traidl-Hoffmann, C

2016-10-01

Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE < 3 kDa) on the human allergic immune response in vivo. Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet-APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet-APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet-APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients. © 2016 John Wiley & Sons Ltd.

Antiallergic effects of ZCR-2060: effect on allergic cutaneous reactions and rhinitis models in mice and rats.

PubMed

Abe, T; Omata, T; Yoshida, K; Segawa, Y; Matsuda, K; Nagai, H

1994-09-01

The antiallergic action of 2-[2-[4-(diphenylmethyl)-1-piperadinyl] ethoxy] benzoic acid maleate (ZCR-2060) was investigated on allergic cutaneous reactions and nasal vascular permeability in mice and rats. ZCR-2060 markedly inhibited immediate allergic cutaneous reactions, including passive cutaneous anaphylaxis (PCA) in rats and mice; histamine-, compound 48/80- and calcium ionophore A 23187-induced cutaneous reactions in rats; and biphasic skin reactions mediated by monoclonal IgE antibody and epicutaneous challenge with antigen in mice, but did not affect 5-hydroxytryptamine-induced cutaneous reaction in rats. The antigen-induced nasal vascular permeability increase in actively and passively sensitized rats and histamine-induced nasal vascular permeability increase in rats (allergic rhinitis model) were clearly inhibited in a dose-dependent fashion by ZCR-2060. Moreover, ZCR-2060 significantly inhibited antigen-induced anaphylactic histamine release from rat peritoneal mast cells and carrageenin-induced paw edema in rats. These results suggest that ZCR-2060 has antiallergic effects on allergic cutaneous reactions and experimental rhinitis, probably due to histamine H1-receptor blockage and the inhibition of histamine release.

Therapeutic Effects of Fermented Red Ginseng in Allergic Rhinitis: A Randomized, Double-Blind, Placebo-Controlled Study

PubMed Central

Jung, Jae-Woo; Ji, Geun-Eog; Park, Myeong-Soo; Song, Woo-Jung; Kim, Min-Hye; Kwon, Jae-Woo; Kim, Tae-Whan; Park, Heung-Woo; Cho, Sang-Heon; Min, Kyung-Up

2011-01-01

Purpose Allergic rhinitis is clinically defined as a disorder of the nose induced by IgE mediated inflammation after allergen exposure of the nasal mucosa. Many reports have stated that Panax ginseng and fermented red ginseng have anti-inflammatory effects, especially against Th2-type inflammation. This study was conducted to evaluate the therapeutic effects of fermented red ginseng in allergic rhinitis. Methods In this 4-week, double-blind, placebo-controlled study, 59 patients with persistent perennial allergic rhinitis were randomly divided into two groups: those receiving fermented red ginseng tablets (experimental group) and those receiving placebo (control group). The primary efficacy variable was the total nasal symptom score (TNSS; rhinorrhea, sneezing, itchy nose, and nasal congestion). Secondary efficacy variables were the Rhinitis Quality of Life (RQoL) score and skin reactivity to inhalant allergens, as determined by the skin prick test. Results There was no significant difference in the TNSS score and TNSS duration score between the experimental and placebo groups in weeks 1, 2, 3, or 4. For nasal congestion, fermented red ginseng was significantly effective (P<0.005), while placebo caused no change. The activity and emotion of RQoL improved markedly secondary to treatment with fermented red ginseng (P<0.05), while placebo caused no change. Additionally, fermented red ginseng reduced skin reactivity to sensitized perennial allergens (P<0.05). Fermented red ginseng was well tolerated. Conclusions Fermented red ginseng improved nasal congestion symptoms and RQoL in patients with perennial allergic rhinitis. PMID:21461249

Th2 Allergic Immune Response to Inhaled Fungal Antigens is Modulated By TLR-4-Independent Bacterial Products

PubMed Central

Allard, Jenna B.; Rinaldi, Lisa; Wargo, Matt; Allen, Gilman; Akira, Shizuo; Uematsu, Satoshi; Poynter, Matthew E.; Hogan, Deborah A.; Rincon, Mercedes; Whittaker, Laurie A.

2009-01-01

SUMMARY Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well know triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens. The consequence of simultaneous exposure to bacterial and fungal products on the lung adaptive immune response has not been explored. Here we show that oropharyngeal aspiration of fungal lysates (Candida albicans, Aspergillus fumigatus) promotes airway eosinophilia, secretion of Th2 cytokines and mucus cell metaplasia. In contrast, oropharyngeal exposure to bacterial lysates (Pseudomonas aeruginosa) promotes airway inflammation characterized by neutrophils, Th1 cytokine secretion and no mucus production. More importantly, administration of bacterial lysates together with fungal lysates deviates the adaptive immune response to a Th1 type associated with neutrophilia and diminished mucus production. The immunomodulatory effect that bacterial lysates have on the response to fungi is TLR4-independent but MyD88 dependent. Thus, different types of microbial products within the airway can alter the host's adaptive immune response, and potentially impact the development of allergic airway disease to environmental fungal antigens. PMID:19224641

Inhibition of allergic encephalomyelitis in marmosets by vaccination with recombinant vaccinia virus encoding for myelin basic protein.

PubMed

Genain, C P; Gritz, L; Joshi, N; Panicali, D; Davis, R L; Whitaker, J N; Letvin, N L; Hauser, S L

1997-11-01

A primary demyelinating form of experimental allergic encephalomyelitis (EAE) resembling human multiple sclerosis (MS) occurs in Callithrix jacchus marmosets following immunization with human white matter. Participation of a T-cell immune response against myelin basic protein (MBP) in this disease model is supported by observations of increased reactivity against MBP in PBMC and of adoptive transfer of an inflammatory form of EAE by MBP-reactive T-cells. To evaluate the effects of ectopic presentation of MBP on marmoset EAE, animals were vaccinated prior to induction of EAE by subcutaneous injection of attenuated strains of vaccinia virus genetically engineered to contain either the entire coding sequence for human MBP (vT15) or the equine herpes virus glycoprotein gH gene (vAbT249). Vaccination with vT15 was followed by transient cytoplasmic and surface membrane expression of MBP in circulating PBMC (15-45 days). The onset of clinical EAE after immunization (pi) was markedly delayed in vT15-vaccinated animals (37-97 days pi, n = 4) compared to vAbT249-vaccinated controls (14-18 days pi, n = 3). Proliferative responses against MBP but not against vaccinia antigens or phytohemagglutinin were suppressed in protected animals. Thus, development of attenuated live viruses carrying genes for myelin antigens could be useful for induction of immunologic tolerance and for modulation of autoimmune demyelination.

Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

PubMed

Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

2013-01-01

A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

An Evaluation of a Natural Language Processing Tool for Identifying and Encoding Allergy Information in Emergency Department Clinical Notes

PubMed Central

Goss, Foster R.; Plasek, Joseph M.; Lau, Jason J.; Seger, Diane L.; Chang, Frank Y.; Zhou, Li

2014-01-01

Emergency department (ED) visits due to allergic reactions are common. Allergy information is often recorded in free-text provider notes; however, this domain has not yet been widely studied by the natural language processing (NLP) community. We developed an allergy module built on the MTERMS NLP system to identify and encode food, drug, and environmental allergies and allergic reactions. The module included updates to our lexicon using standard terminologies, and novel disambiguation algorithms. We developed an annotation schema and annotated 400 ED notes that served as a gold standard for comparison to MTERMS output. MTERMS achieved an F-measure of 87.6% for the detection of allergen names and no known allergies, 90% for identifying true reactions in each allergy statement where true allergens were also identified, and 69% for linking reactions to their allergen. These preliminary results demonstrate the feasibility using NLP to extract and encode allergy information from clinical notes. PMID:25954363

Females have stronger neurogenic response than males after non-specific nasal challenge in patients with seasonal allergic rhinitis.

PubMed

Tomljenovic, Dejan; Baudoin, Tomislav; Megla, Zeljka Bukovec; Geber, Goran; Scadding, Glenis; Kalogjera, Livije

2018-07-01

Epidemiological studies show female predominance in the prevalence of non- allergic rhinitis (NAR) and local allergic rhinitis (LAR). Experimental studies show female patients with allergic rhinitis (AR) demonstrate higher levels of sensitivity to irritants and airway hyperresponsiveness than males. Bronchial asthma shows female predominance in post-puberty patients, and gender interaction with severe asthma endotypes. Fibromyalgia, chronic fatigue syndrome, migraine and chronic cough, syndromes, which are commonly related to neurokinin substance P (SP) in the literature, also show strong female predominance. Studies have demonstrated that sex hormones, primarily oestrogens, affect mast cell activation. Mast cell proteases can amplify neurogenic inflammatory responses including the release of SP. Based on human epidemiological data and animal experimental data we hypothesized that female patients have different interaction between mast cell activation and neurogenic inflammation, i.e. substance P release, resulting in a different nasal symptom profile. To test the hypothesis we performed allergen and non-specific nasal challenges in patients with seasonal allergic rhinitis (SAR) out of season and looked for gender differences in subjective and objective responses. The interaction between subjective and objective reactivity was evaluated through the comparison of subjective symptom scores, concentrations of neurokinin substance P (SP) and cellular markers in nasal lavages after low doses of nasal allergen challenges. Female allergic subjects tended to have higher substance P (SP) concentrations both before and after non-specific challenges. The difference between post-allergen and post - hypertonic saline (HTS) challenge was highly significant in female patients (p = 0.001), while insignificant in male subjects (p = 0.14). Female patients had significantly stronger burning sensation after HTS challenge than male. These data indicate difference in the interaction between inflammatory cells and the neurogenic response, which is gender- related, and which may affect symptom profiles after challenges. Different regulation of neurogenic inflammation in females may have impact on symptoms and endotyping in respiratory disorders, not only in allergic rhinitis, but also asthma, chronic rhinosinusitis and irritant -induced cough. Copyright © 2018 Elsevier Ltd. All rights reserved.

The aryl hydrocarbon receptor modulates acute and late mast cell responses.

PubMed

Sibilano, Riccardo; Frossi, Barbara; Calvaruso, Marco; Danelli, Luca; Betto, Elena; Dall'Agnese, Alessandra; Tripodo, Claudio; Colombo, Mario P; Pucillo, Carlo E; Gri, Giorgia

2012-07-01

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics as well as physiological ligands. These compounds may modulate inflammatory responses and contribute to the rising prevalence of allergic diseases observed in industrialized countries. Mast cells (MCs), located within tissues at the boundary of the external environment, represent a potential target of AhR ligands. In this study, we report that murine and human MCs constitutively express AhR, and its activation by the high-affinity ligand 6-formylindolo[3,2-b]carbazole (FICZ) determines a boost in degranulation. On the contrary, repeated exposure to FICZ inhibits MC degranulation. Accordingly, histamine release, in an in vivo passive systemic anaphylactic model, is exacerbated by a single dose and is attenuated by repetitive stimulation of AhR. FICZ-exposed MCs produce reactive oxygen species and IL-6 in response to cAMP-dependent signals. Moreover, AhR-activated MCs produce IL-17, a critical player in chronic inflammation and autoimmunity, suggesting a novel pathway for MC activation in the pathogenesis of these diseases. Indeed, histological analysis of patients with chronic obstructive pulmonary disease revealed an enrichment in AhR/IL-6 and AhR/IL-17 double-positive MCs within bronchial lamina propria. Thus, tissue-resident MCs could translate external chemical challenges through AhR by modulating allergic responses and contributing to the generation of inflammation-related diseases.

Anti-allergic activity of standardized extract of Albizia lebbeck with reference to catechin as a phytomarker.

PubMed

Venkatesh, Pichairajan; Mukherjee, Pulok K; Kumar, Nanjappan Satheesh; Bandyopadhyay, Arun; Fukui, Hiroyuki; Mizuguchi, Hiroyuki; Islam, Nurul

2010-06-01

The major groups of phytonutrients found in plants include polyphenols, flavonoids, terpenes, amines, etc., all of which are observed to have potential anti-allergic activity. In this study, we evaluated the anti-allergic activity of the standardized extract of Albizia lebbeck with respect to the catechin, a polyphenolic phytomarker. The percentage of catechin in the ethanolic extract was found to be 14.72 mg/g. We administered Albizia lebbeck (50-300 mg/kg) and 50 mg/kg of catechin to mice to evaluate the mast cell stabilization and estimation of histamine elevation in the plasma. Results support the conclusion that Albizia lebbeck at different concentrations has got potent mast cell stabilizing property and the IC(50) value of Albizia lebbeck was found to be 85 microg/ml. This inhibitory potential of catechin from Albizia lebbeck is perhaps due to modulation of two important effector's functions, histamine release and cytokine expression of antigen -IgE activated mast cells.

[Specific immunotherapy. Hyposensitization with allergens].

PubMed

Wedi, B; Kapp, A

2004-04-01

Successful allergen-specific immunotherapy (SIT) induces complex immunologic chan-ges resulting in reduced allergic inflammatory reactions. SIT has long-term effects in mild forms of inhalant allergies and is effective even when standard pharmacotherapy fails. Moreover, the risk to develop additional allergic sensitizations and the development of asthma is significantly reduced in children with allergic rhinitis. SIT is the treatment of choice in patients with systemic reactions to hymenoptera venoms. Although the exact effector mechanisms of SIT still have to be clarified, the most probable effect is a modulation of regulatory T cells associated with a switch of allergen-specific B-cells towards IgG4 production. The critical point to insure efficacy and safety is the selection of patients and allergens, task best performed by a specialist trained in allergology. Further details are available in the position papers of the German allergy societies - DGAI(Deutsche Gesellschaft fiir Allergologie und Klinische Immunologie) and ADA (Arzte-verband Deutscher Allergologen) - which can be found at www.dgaki.de.

Helminths: Immunoregulation and Inflammatory Diseases—Which Side Are Trichinella spp. and Toxocara spp. on?

PubMed Central

Aranzamendi, Carmen; Sofronic-Milosavljevic, Ljiljana; Pinelli, Elena

2013-01-01

Macropathogens, such as multicellular helminths, are considered masters of immunoregulation due to their ability to escape host defense and establish chronic infections. Molecular crosstalk between the host and the parasite starts immediately after their encounter, which influences the course and development of both the innate and adaptive arms of the immune response. Helminths can modulate dendritic cells (DCs) function and induce immunosuppression which is mediated by a regulatory network that includes regulatory T (Treg) cells, regulatory B (Breg) cells, and alternatively activated macrophages (AAMs). In this way, helminths suppress and control both parasite-specific and unrelated immunopathology in the host such as Th1-mediated autoimmune and Th2-mediated allergic diseases. However, certain helminths favour the development or exacerbation of allergic responses. In this paper, the cell types that play an essential role in helminth-induced immunoregulation, the consequences for inflammatory diseases, and the contrasting effects of Toxocara and Trichinella infection on allergic manifestations are discussed. PMID:23365718

The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation.

PubMed

Zaiss, Mario M; Rapin, Alexis; Lebon, Luc; Dubey, Lalit Kumar; Mosconi, Ilaria; Sarter, Kerstin; Piersigilli, Alessandra; Menin, Laure; Walker, Alan W; Rougemont, Jacques; Paerewijck, Oonagh; Geldhof, Peter; McCoy, Kathleen D; Macpherson, Andrew J; Croese, John; Giacomin, Paul R; Loukas, Alex; Junt, Tobias; Marsland, Benjamin J; Harris, Nicola L

2015-11-17

Intestinal helminths are potent regulators of their host's immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production. Transfer of the Hpb-modified microbiota alone was sufficient to mediate protection against allergic asthma. The helminth-induced anti-inflammatory cytokine secretion and regulatory T cell suppressor activity that mediated the protection required the G protein-coupled receptor (GPR)-41. A similar alteration in the metabolic potential of intestinal bacterial communities was observed with diverse parasitic and host species, suggesting that this represents an evolutionary conserved mechanism of host-microbe-helminth interactions. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells.

PubMed Central

Delneste, Y; Jeannin, P; Gosset, P; Lassalle, P; Cardot, E; Tillie-Leblond, I; Joseph, M; Pestel, J; Tonnel, A B

1995-01-01

Adhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not. E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergics compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-1 expression were inhibited by anti-interferon-gamma (IFN-gamma) antibodies. Enhanced production of IL-4 and IFN-gamma was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site. PMID:7542574

Cornuside inhibits mast cell-mediated allergic response by down-regulating MAPK and NF-κB signaling pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Liangchang; Jin, Guangyu; Jiang, Jingzhi

Aims: The present study is to investigate the effect of cornuside on mast cell-mediated allergic response, as well as its possible mechanisms of action. Methods: To test the anti-allergic effects of cornuside in vivo, local extravasation was induced by local injection of anti-dinitrophenyl immunoglobulin E (IgE) followed by intravenous antigenic challenge in passive cutaneous anaphylaxis model rats. Mast cell viability was determined using MTT assay. Histamine content from rat peritoneal mast cells was measured by the radioenzymatic method. To investigate the mechanisms by which cornuside affects the reduction of histamine release, the levels of calcium uptake were measured. To examine whethermore » cornuside affects the expression of pro-inflammatory cytokines, Western blotting and ELISA were carried out. Results: Oral administration of cornuside inhibited passive cutaneous anaphylaxis in rats. Presence of cornuside attenuated IgE-induced histamine release from rat peritoneal mast cells. The inhibitory effect of cornuside on histamine release was mediated by the modulation of intracellular calcium. In addition, cornuside decreased phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-stimulated production and secretion of pro-inflammatory cytokines such as TNF-α and IL-6 in human mast cells. The inhibitory effect of cornuside on pro-inflammatory cytokines was dependent on nuclear factor-κB and p38 mitogen-activated protein kinase. Conclusions: The present study provides evidence that cornuside inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. Furthermore, in vivo and in vitro anti-allergic effects of cornuside suggest a possible therapeutic application of this agent in inflammatory allergic diseases.« less

Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2.

PubMed

Koth, Laura L; Rodriguez, Madeleine W; Bernstein, Xin Liu; Chan, Salina; Huang, Xiaozhu; Charo, Israel F; Rollins, Barrett J; Erle, David J

2004-09-15

Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2.

Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

PubMed Central

Koth, Laura L; Rodriguez, Madeleine W; Bernstein, Xin Liu; Chan, Salina; Huang, Xiaozhu; Charo, Israel F; Rollins, Barrett J; Erle, David J

2004-01-01

Background Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. Methods To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. Results We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. Conclusion We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2. PMID:15377395

American Academy of Asthma, Allergy and Immunology--55th annual meeting. 26 February-3 March 1999, Orlando, FL, USA.

PubMed

Lieberman, P

1999-05-01

This was a particularly comprehensive gathering of investigators and clinicians interested in the field of allergy, asthma and immunology. The meeting presented information ranging from basic immunological research to the clinical trials of drugs already available for treatment in the US today. There were 984 original oral and poster presentations and over 100 symposia, seminars and workshops. The plenary sessions involved sections on allergic inflammation, immune modulation, chemokine receptors, the origins of asthma, the diagnosis and management of food and drug reactions, the environmental influences on allergic diseases, and dermatological diseases. There were approximately 500 faculty members who presented new data or participated in lectures, seminars or workshops.

Effects of Air Pollutants on Development of Allergic Immune Responses in the Respiratory Tract

PubMed Central

Gershwin, Laurel J.

2003-01-01

The increased incidence of allergic asthma in the human population worldwide has stimulated many explanatory theories. A concomitant decrease in air quality leads to epidemiological and laboratory-based studies to demonstrate a link between air pollutants and asthma. Specifically, ozone, environmental tobacco smoke, and diesel exhaust are associated with enhancement of respiratory allergy to inhaled allergens. This review summarizes the state of the knowledge, both human epidemiology and laboratory animal experiments, linking air pollution to allergy. Critical issues involve development of the lung and the fetal immune response, and the potential for substances like ozone and ETS in the air to modulate early immune responses with lifelong consequences. PMID:14768942

Formulation considerations of intranasal corticosteroids for the treatment of allergic rhinitis.

PubMed

Meltzer, Eli O

2007-01-01

To examine how various aspects of an intranasal corticosteroid (INS) formulation may influence the efficacy, tolerability, and patient preference and adherence to INS therapy. A PubMed search of the literature was conducted for studies on allergic rhinitis published between January 1977 and January 2006 using the keywords intranasal corticosteroid, preservatives, benzalkonium chloride, and tonicity. Prospective studies, retrospective studies, and case reports were selected for inclusion in this review. Currently available INSs are effective first-line treatments for allergic rhinitis. Differences in patient preference for a particular INS are largely attributable to sensory attributes of the nasal spray, which arise from characteristics of the formulation. Additives and preservatives can cause tolerability issues by irritating the mucosal membranes and causing nasal drying, or they can confer an unpleasant odor or taste to an INS formulation. The relative osmotic pressure, or tonicity, of an INS can modulate nasal absorption and retention, thereby potentially influencing the clinical efficacy. Characteristics such as delivery device and spray volume can affect a patient's perception and experience with a particular INS. Newer INSs, such as ciclesonide, are in development for the treatment of allergic rhinitis, and consideration of the formulation characteristics of these agents is an important part of the development process. INSs are an effective treatment option for patients with allergic rhinitis; however, there is room for formulation improvement. Optimization of formulation may increase the efficacy, tolerability, and patient preference and adherence to INSs.

Dietary, nondigestible oligosaccharides and Bifidobacterium breve M-16V suppress allergic inflammation in intestine via targeting dendritic cell maturation.

PubMed

de Kivit, Sander; Kostadinova, Atanaska I; Kerperien, JoAnn; Morgan, Mary E; Muruzabal, Veronica Ayechu; Hofman, Gerard A; Knippels, Leon M J; Kraneveld, Aletta D; Garssen, Johan; Willemsen, Linette E M

2017-07-01

Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V ( Bb ) (GF/ Bb ) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/ Bb modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (T reg ) frequency in the small intestinal lamina propria (SI-LP). BALB/c mice were fed GF/ Bb during oral OVA sensitization. DC and T cell phenotype were determined in SI-LP mononuclear cells using flow cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC-conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/ Bb reduced allergic symptoms and enhanced serum galectin-9 levels, while suppressing activation, restoring phagocytic capacity, and normalizing CD103 expression of SI-LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium suppressed moDC activation in a galectin-9-dependent manner. Besides suppression of SI-LP DC activation, dietary GF/ Bb also lowered the frequency of activated Th2 cells, while enhancing T reg in the SI-LP of OVA-allergic mice compared to the control diet. Dietary intervention with GF/ Bb enhances galectin-9 and suppresses allergic symptoms of OVA-allergic mice in association with reduced intestinal DC and Th2 activation and increased T reg frequency in these mice. © Society for Leukocyte Biology.

Skincare products containing low concentrations of formaldehyde detected by the chromotropic acid method cannot be safely used in formaldehyde-allergic patients.

PubMed

Hauksson, I; Pontén, A; Gruvberger, B; Isaksson, M; Engfeldt, M; Bruze, M

2016-02-01

Formaldehyde is a well-known contact sensitizer. Formaldehyde releasers are widely used preservatives in skincare products. It has been found that formaldehyde at concentrations allowed by the European Cosmetics Directive can cause allergic contact dermatitis. However, we still lack information on whether formaldehyde at low concentrations affects dermatitis in formaldehyde-allergic individuals. To study the effects of low concentrations of formaldehyde on irritant contact dermatitis in formaldehyde-allergic individuals. Fifteen formaldehyde-allergic individuals and a control group of 12 individuals without contact allergy to formaldehyde and formaldehyde releasers were included in the study. The individuals performed the repeated open application test (ROAT) during 4 weeks with four different moisturizers releasing formaldehyde in concentrations that had been determined as > 40, 20-40, 2·5-10 and 0 p.p.m. by the chromotropic acid (CA) spot test. Dimethyloldimethylhydantoin was used as a formaldehyde releaser in the moisturizers. The ROAT was performed on areas of experimentally induced sodium lauryl sulfate dermatitis. The study was double blind, controlled and randomized. Nine of the 15 formaldehyde-allergic individuals had reappearance or worsening of dermatitis on the areas that were treated with moisturizers containing formaldehyde. No such reactions were observed in the control group (P < 0·001) or for the moisturizers without formaldehyde in the formaldehyde-allergic individuals (P < 0·001). Our results demonstrate that the low concentrations of formaldehyde often found in skincare products by the CA method are sufficient to worsen an existing dermatitis in formaldehyde-allergic individuals. © 2015 British Association of Dermatologists.

Probiotics for the prevention or treatment of allergic diseases.

PubMed

Prescott, Susan L; Björkstén, Bengt

2007-08-01

This review addresses the effects of probiotic bacteria on immune development and the role in the treatment and prevention of allergic disease. Although there is a sound theoretical basis for anticipating benefits, there are currently insufficient data to recommend probiotics as a part of standard therapy in any allergic conditions. Furthermore, although there have been several studies to show a benefit in prevention of atopic eczema, other studies have failed to support this. None of the studies has shown any clear preventive effect on sensitization, nor any allergic disease other than eczema. The term "probiotic" is often used loosely to include bacterial strains with little documented immunomodulatory capacity or controlled studies to support the claims. It is not known whether effects in experimental systems have any clinical relevance. Finally, very little is known about this large, complex internal ecosystem. Explanations for the varied results between studies include host factors (including genetic differences in microbial responses and allergic predisposition) and other environmental factors, such as general microbial burden, individual microbiota, diet (including consumption of prebiotic substances), and treatment with antibiotics. As more studies are completed, these factors are likely to make robust meta-analyses problematic to perform.

Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

PubMed

Duez, C; Gras-Masse, H; Hammad, H; Akoum, H; Didierlaurent, A; André, C; Tonnel, A B; Pestel, J

2001-01-01

We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

PubMed

Pryce, Gareth; Ahmed, Zubair; Hankey, Deborah J R; Jackson, Samuel J; Croxford, J Ludovic; Pocock, Jennifer M; Ledent, Catherine; Petzold, Axel; Thompson, Alan J; Giovannoni, Gavin; Cuzner, M Louise; Baker, David

2003-10-01

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.

Effect of pregnancy on experimental allergic encephalomyelitis in guinea pigs and rats.

PubMed

Keith, A B

1978-10-01

Pregnancy in guinea pigs and rats exerted a suppressive influence on the development of experimental allergic encephalomyelitis (EAE). Early or late stages in pregnancy had a similar effect in delaying the onset of EAE, a greater delay being observed in pregnant guinea pigs with full term pregnancies. However, the suppressive effect in the majority of animals was only temporary and when they developed the disease the clinical severity was then similar to that in the controls. Clinical symptoms of EAE, in guinea pigs that did not maintain their pregnancy, developed soon after abortion or resorption and these animals deteriorated rapidly. Histologic lesions were markedly enhanced with prominent demyelination in the majority of guinea pigs that were sensitised when pregnant.

Immunomodulation of allergic autocytotoxicity in bronchial asthma by a bacterial lysate--Broncho-Vaxom.

PubMed

Podleski, W K

1985-01-01

The direct and antibody-dependent allergic autocytotoxicity (ACT) response, mediated by food antigens and its immunoregulation with bacterial lysate of the eight most common pathogens of the upper respiratory tract--Broncho-Vaxom (BX), was investigated in fifteen bronchial asthma patients and eight normal control individuals. Under the described experimental conditions, the BX inhibits ACT response in vitro. In analyzing the mechanism of this effect, the enhancement of T suppressor cells by BX was under consideration.

mTOR complexes differentially orchestrates eosinophil development in allergy.

PubMed

Zhu, Chen; Xia, Lixia; Li, Fei; Zhou, Lingren; Weng, Qingyu; Li, Zhouyang; Wu, Yinfang; Mao, Yuanyuan; Zhang, Chao; Wu, Yanping; Li, Miao; Ying, Songmin; Chen, Zhihua; Shen, Huahao; Li, Wen

2018-05-02

Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.

Oral supplementation with areca-derived polyphenols attenuates food allergic responses in ovalbumin-sensitized mice

PubMed Central

2013-01-01

Background Arecae semen, the dried slice of areca nuts, is a traditional Chinese medicine used to treat intestinal parasitosis, rectal tenesmus and diarrhea. Areca nuts contain a rich amount of polyphenols that have been shown to modulate the functionality of mast cells and T cells. The objective of this study is to investigate the effect of polyphenol-enriched areca nut extracts (PANE) against food allergy, a T cell-mediated immune disorder. Methods BALB/c mice were left untreated or administered with PANE (0.05% and 0.1%) via drinking water throughout the entire experiment. The mice were sensitized with ovalbumin (OVA) twice by intraperitoneal injection, and then repeatedly challenged with OVA by gavage to induce food allergic responses. Results PANE administration attenuated OVA-induced allergic responses, including the occurrence of diarrhea and the infiltration and degranulation of mast cells in the duodenum. The serum level of OVA-specific IgE and the expression of interleukin-4 in the duodenum were suppressed by PANE treatment. In addition, PANE administration induced Gr-1+, IL-10+ and Gr-1+IL-10+ cells in the duodenum. Conclusion These results demonstrate that oral intake of areca-derived polyphenols attenuates food allergic responses accompanied with a decreased Th2 immunity and an enhanced induction of functional myeloid-derived suppressor cells. PMID:23816049

Purified aged garlic extract modulates allergic airway inflammation in BALB/c mice.

PubMed

Zare, Ahad; Farzaneh, Parvaneh; Pourpak, Zahra; Zahedi, Fatemeh; Moin, Mostafa; Shahabi, Shahram; Hassan, Zuhair M

2008-09-01

Garlic is known as a potent spice and a medicinal herb with broad therapeutic properties ranging from antibacterial to anticancer and anticoagulant. Our previous studies have shown some immunoregulatory effects for aged garlic extract, suggesting a key role for 14-kD glycoprotein of garlic in shifting the cytokine pattern to T helper-1. In present study, we investigated the effect of 1, 2, and 3 times intraperitoneal injections of aged garlic extract on an established allergic airway inflammation in murine model (BALB/c mice). The garlic extract, isolated by biochemical method, includes proteins precipitation by ammonium sulfate. After injection of the aged garlic extract, IFN-, anti allergen specific IgE and IgG1 were measured in lavage and serum by ELISA and histological assessment was performed on the lung tissues. The results indicated that three-time intra peritoneal injections of the aged garlic extract caused a significant decrease in the hallmark criteria of allergic airway inflammation levels which included eosinophil percentage in lavage, peribronchial lung eosinophils, IgG1 level in lavage and serum, mucous producing goblet cells grade and peribronchial and perivascular inflammation. Our findings in the present research suggested that aged garlic extract has the potential of attenuation of inflammatory features of allergic airway inflammation in murine model.

Modulation of pulmonary inflammatory responses and anti-microbial defenses in mice exposed to diesel exhaust

EPA Science Inventory

Abstract: Diesel exhaust (DE) is a major component of urban air pollution and has been shown to increase the severity of infectious and allergic lung disease. The purpose of this study was to evaluate the effects of DE exposure on pulmonary inflammation, mediator production and ...

Effect of treatment with geraniol on ovalbumin-induced allergic asthma in mice.

PubMed

Xue, Zheng; Zhang, Xin-Guang; Wu, Jie; Xu, Wan-Chao; Li, Li-Qing; Liu, Fei; Yu, Jian-Er

2016-06-01

Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate. To evaluate the antiasthma activity of geraniol and investigate its underlying molecular mechanisms. In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with geraniol (100 or 200 mg/kg) or a vehicle control, during ovalbumin challenge. Treatment of ovalbumin-sensitized/challenged mice with geraniol significantly decreased airway hyperresponsiveness to inhaled methacholine. Geraniol treatment reduced eotaxin levels in bronchoalveolar lavage fluid and attenuated infiltration of eosinophils induced by ovalbumin. Geraniol treatment reduced TH2 cytokines (including interleukins 4, 5, and 13), increased TH1 cytokine interferon γ in bronchoalveolar lavage fluid, and reduced ovalbumin-specific IgE in serum. In addition, treatment of ovalbumin-sensitized/challenged mice with geraniol enhanced T-bet (TH1 response) messenger RNA expression and reduced GATA-3 (TH2 response) messenger RNA expression in lungs. Furthermore, treatment of ovalbumin -sensitized/challenged mice with geraniol further enhanced Nrf2 protein expression and activated Nrf2-directed antioxidant pathways, such as glutamate-cysteine ligase, superoxide dismutase, and glutathione S-transferase, and enhanced formation of reduced glutathione and reduced formation of malondialdehyde in lungs. Geraniol attenuated important features of allergic asthma in mice, possibly through the modulation of TH1/TH2 balance and activation the of Nrf2/antioxidant response element pathway. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Developments in the field of allergy mechanisms in 2015 through the eyes of Clinical & Experimental Allergy.

PubMed

Roberts, G; Boyle, R; Bryce, P J; Crane, J; Hogan, S P; Saglani, S; Wickman, M; Woodfolk, J A

2016-10-01

In the first of two papers we described the development in the field of allergy mechanisms as described by Clinical and Experimental Allergy in 2015. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered. A second paper will cover clinical aspects. © 2016 John Wiley & Sons Ltd.

Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice.

PubMed

Yang, Bo; Xiao, Liang; Liu, Sheng; Liu, Xiaoyu; Luo, Yan; Ji, Qiongmei; Yang, Pingchang; Liu, Zhigang

2017-01-01

Environmental factor-induced alterations in intestinal microbiota have been demonstrated to be associated with increasing prevalence of food allergy. However, it is not clear to what extent oral administration of probiotics can affect gut microbiota composition, thus inhibiting food allergy development. Using ovalbumin (OVA)-sensitized murine model, it was demonstrated that probiotics ameliorated allergic symptoms, including reducing OVA specific-IgE, and -IgG1 levels in the serum, Th2 cytokines release in spleen, and occurrence of diarrhea. Moreover, 16S rRNA analysis showed that the probiotics-mediated protection was conferred by an enrichment of Coprococcus and Rikenella . The present study supports the theory that probiotics can treat food allergy by modulating specific genera of the gut microbiota.

Therapeutic potential of larval excretory/secretory proteins of the pig whipworm Trichuris suis in allergic disease.

PubMed

Ebner, F; Hepworth, M R; Rausch, S; Janek, K; Niewienda, A; Kühl, A; Henklein, P; Lucius, R; Hamelmann, E; Hartmann, S

2014-11-01

Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability to induce immunoregulatory pathways in their hosts. In particular, administration of ova from the pig whipworm Trichuris suis (T. suis; TSO) has been proposed for the treatment of allergic, inflammatory and autoimmune disorders. Despite these advances, the biological pathways through which TSO therapy modulates the host immune system in the context of human disease remain undefined. We characterized the dominant proteins present in the excretory/secretory (E/S) products of first-stage (L1) T. suis larvae (Ts E/S) using LC-MS/MS analysis and examined the immunosuppressive properties of whole larval Ts E/S in vitro and in a murine model of allergic airway disease. Administration of larval Ts E/S proteins in vivo during the allergen sensitization phase was sufficient to suppress airway hyperreactivity, bronchiolar inflammatory infiltrate and allergen-specific IgE production. Three proteins in larval Ts E/S were unambiguously identified. The immunomodulatory function of larval Ts E/S was found to be partially dependent on the immunoregulatory cytokine IL-10. Taken together, these data demonstrate that the released proteins of larval T. suis have significant immunomodulatory capacities and efficiently dampen allergic airway hyperreactivity. Thus, the therapeutic potential of defined larval E/S proteins should be exploited for the treatment of human allergic disorders. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intranasal exposure to monoclonal antibody Fab fragments to Japanese cedar pollen Cry j1 suppresses Japanese cedar pollen‐induced allergic rhinitis

PubMed Central

Mizutani, N

2016-01-01

Background and Purpose Fab fragments (Fabs) of antibodies have the ability to bind to specific allergens but lack the Fc portion that exerts effector functions via binding to receptors including FcεR1 on mast cells. In the present study, we investigated whether intranasal administration of the effector function‐lacking Fabs of a monoclonal antibody IgG1 (mAb, P1‐8) to the major allergen Cry j1 of Japanese cedar pollen (JCP) suppressed JCP‐induced allergic rhinitis in mice. Experimental Approach Balb/c mice sensitized with JCP on days 0 and 14 were challenged intranasally with the pollen on days 28, 29, 30 and 35. Fabs prepared by the digestion of P1‐8 with papain were also administered intranasally 15 min before each JCP challenge. Key Results Intranasal administration of P1‐8 Fabs was followed by marked suppression of sneezing and nasal rubbing in mice with JCP‐induced allergic rhinitis. The suppression of these allergic symptoms by P1‐8 Fabs was associated with decreases in mast cells and eosinophils and decreased hyperplasia of goblet cells in the nasal mucosa. Conclusions and Implications These results demonstrated that intranasal exposure to P1‐8 Fabs was effective in suppressing JCP‐induced allergic rhinitis in mice, suggesting that allergen‐specific mAb Fabs might be used as a tool to regulate allergic pollinosis. PMID:26895546

Fragrance sensitisers: Is inhalation an allergy risk?

PubMed

Basketter, David; Kimber, Ian

2015-12-01

It is well established that some fragrance substances have the potential to cause skin sensitisation associated with the development of allergic contact dermatitis (ACD). Fragrances are invariably relatively volatile leading to the consideration that inhalation of fragrances might be a relevant route for either the induction of allergic sensitisation or the elicitation of allergic reactions. Moreover, there has been increasing recognition that allergic sensitisation of the respiratory tract can be induced by topical exposure to certain chemical allergens. Here the central question addressed is whether inhalation exposure to fragrance allergens has the potential to cause skin and/or respiratory sensitisation via the respiratory tract, or elicit allergic symptoms in those already sensitised. In addressing those questions, the underlying immunobiology of skin and respiratory sensitisation to chemicals has been reviewed briefly, and the relevant experimental and clinical evidence considered. The essential mechanistic differences between skin and respiratory allergy appear consistent with other sources of information, including the phenomenon of ACD that can arise from topical exposure to airborne allergens, but in the absence of accompanying respiratory effects. The conclusion is that, in contrast to topical exposure (including topical exposure to airborne material), inhalation of fragrance sensitisers does not represent a health risk with respect to allergy. Copyright © 2015 Elsevier Inc. All rights reserved.

A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic treatment of asthma.

PubMed

Méndez-Enríquez, E; Medina-Tamayo, J; Soldevila, G; Fortoul, T I; Anton, B; Flores-Romo, L; García-Zepeda, E A

2014-05-01

Allergic asthma is a chronic inflammatory disease characterized by the accumulation of eosinophils, Th2 cells and mononuclear cells in the airways, leading to changes in lung architecture and subsequently reduced respiratory function. We have previously demonstrated that CDIP-2, a chemokine derived peptide, reduced in vitro chemotaxis and decreased cellular infiltration in a murine model of allergic airway inflammation. However, the mechanisms involved in this process have not been identified yet. Now, we found that CDIP-2 reduces chemokine-mediated functions via interactions with CCR1, CCR2 and CCR3. Moreover, using bone marrow-derived eosinophils, we demonstrated that CDIP-2 modifies the calcium fluxes induced by CCL11 and down-modulated CCR3 expression. Finally, CDIP-2 treatment in a murine model of OVA-induced allergic airway inflammation reduced leukocyte recruitment and decreases production of cytokines. These data suggest that chemokine-derived peptides represent new therapeutic tools to generate more effective antiinflammatory drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

8-oxoguanine DNA Glycosylase 1-Deficiency Modifies Allergic Airway Inflammation by Regulating STAT6 and IL-4 in Cells and in Mice

PubMed Central

Li, Guoping; Yuan, Kefei; Yan, Chunguang; Fox, John; Gaid, Madeleine; Breitwieser, Wayne; Bansal, Arvind K.; Zeng, Huawei; Gao, Hongwei; Wu, Min

2013-01-01

8-oxoguanine-DNA glycosylase (OGG-1) is a base excision DNA repair enzyme; however, its function in modulating allergic diseases remains undefined. Using OGG-1 knockout (KO) mice, we show that this protein impacts allergic airway inflammation following sensitization and challenge by ovalbumin (OVA). OGG-1 KO mice exhibited less inflammatory cell infiltration and reduced oxidative stress in the lungs after OVA challenge compared to WT mice. The KO phenotype included decreased IL-4, IL-6, IL-10, and IL-17 in lung tissues. In addition, OGG-1 KO mice showed decreased expression and phosphorylation of STAT6 as well as NF-κB. Down-regulation of OGG-1 by siRNA lowered ROS and IL-4 levels but increased INF-γ production in cultured epithelial cells following exposure to house dust mite (HDM) extracts. OGG-1 may affect the levels of oxidative stress and proinflammatory cytokines during asthmatic conditions. OGG-1-deficiency negatively regulates allergen-induced airway inflammatory response. PMID:22100973

Rhinoviruses, Allergic Inflammation, and Asthma

PubMed Central

Gavala, Monica; Bertics, Paul J.; Gern, James E.

2011-01-01

Summary Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma. PMID:21682739

Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.

PubMed

Kirstein, Frank; Nieuwenhuizen, Natalie E; Jayakumar, Jaisubash; Horsnell, William G C; Brombacher, Frank

2016-06-01

TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood. This study defines the requirements for IL-4Rα-responsive CD4(+) T cells and the IL-4Rα ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease. Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Rα-deficient BALB/c mice (Lck(cre)IL-4Rα(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13. During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Rα-responsive CD4(+) T cells. Deficiency in IL-4Rα-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia. IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Toxoplasma gondii infection blocks the development of allergic airway inflammation in BALB/c mice.

PubMed

Fenoy, I; Giovannoni, M; Batalla, E; Martin, V; Frank, F M; Piazzon, I; Goldman, A

2009-02-01

There is a link between increased allergy and a reduction of some infections in western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofaecal and foodborne microbes such as Toxoplasma gondii. Infection with T. gondii induces a strong cell-mediated immunity with a highly polarized T helper type 1 (Th1) response in early stages of infection. Using a well-known murine model of allergic lung inflammation, we sought to investigate whether T. gondii infection could modulate the susceptibility to develop respiratory allergies. Both acute and chronic infection with T. gondii before allergic sensitization resulted in a diminished allergic inflammation, as shown by a decrease in bronchoalveolar lavage (BAL) eosinophilia, mononuclear and eosinophil cell infiltration around airways and vessels and goblet cell hyperplasia. Low allergen-specific immunoglobulin (Ig)E and IgG1 and high levels of allergen-specific IgG2a serum antibodies were detected. A decreased interleukin (IL)-4 and IL-5 production by lymph node cells was observed, while no antigen-specific interferon-gamma increase was detected. Higher levels of the regulatory cytokine IL-10 were found in BAL from infected mice. These results show that both acute and chronic parasite infection substantially blocked development of airway inflammation in adult BALB/c mice. Our results support the hypothesis that T. gondii infection contributes to protection against allergy in humans.

Toxoplasma gondii infection blocks the development of allergic airway inflammation in BALB/c mice

PubMed Central

Fenoy, I; Giovannoni, M; Batalla, E; Martin, V; Frank, F M; Piazzon, I; Goldman, A

2009-01-01

There is a link between increased allergy and a reduction of some infections in western countries. Epidemiological data also show that respiratory allergy is less frequent in people exposed to orofaecal and foodborne microbes such as Toxoplasma gondii. Infection with T. gondii induces a strong cell-mediated immunity with a highly polarized T helper type 1 (Th1) response in early stages of infection. Using a well-known murine model of allergic lung inflammation, we sought to investigate whether T. gondii infection could modulate the susceptibility to develop respiratory allergies. Both acute and chronic infection with T. gondii before allergic sensitization resulted in a diminished allergic inflammation, as shown by a decrease in bronchoalveolar lavage (BAL) eosinophilia, mononuclear and eosinophil cell infiltration around airways and vessels and goblet cell hyperplasia. Low allergen-specific immunoglobulin (Ig)E and IgG1 and high levels of allergen-specific IgG2a serum antibodies were detected. A decreased interleukin (IL)-4 and IL-5 production by lymph node cells was observed, while no antigen-specific interferon-γ increase was detected. Higher levels of the regulatory cytokine IL-10 were found in BAL from infected mice. These results show that both acute and chronic parasite infection substantially blocked development of airway inflammation in adult BALB/c mice. Our results support the hypothesis that T. gondii infection contributes to protection against allergy in humans. PMID:19032550

Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice

DOE PAGES

Ballester, Marie; Jeanbart, Laura; de Titta, Alexandre; ...

2015-09-21

An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatorymore » therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.« less

An Overlook to the Characteristics and Roles Played by Eotaxin Network in the Pathophysiology of Food Allergies: Allergic Asthma and Atopic Dermatitis.

PubMed

Ahmadi, Zahra; Hassanshahi, Gholamhossein; Khorramdelazad, Hossein; Zainodini, Nahid; Koochakzadeh, Leila

2016-06-01

Investigations revealed substantial parts accomplished by chemokines specifically eotaxins and their specific receptors. They are functionally involved in the modulation of the pathologic state of tissue inflammation which is as a result of allergic reactions. Chemokines as small proteins with approximately 8-10 kDa molecular weight are considered and fit in the bigger family of cytokines, containing basic heparin-binding polypeptide mediators. Chemokines actively interfere in the processes of selective, oriented leukocyte (including eosinophil) recruitment. As eminent from their name, more specifically, eotaxins are specialized for eosinophils' oriented locomotion toward allergic inflamed regions. To date, three members are defined for eotaxin subfamily as follows: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), all of them bind to and activate CCR3 but have a low level of homology and appear to exhibit different physiological potentials. Allergy is described as a clinical state in which a pathologic hypersensitivity reaction is always initiated throughout an immunologic mechanism; similar to other immunologic reactions, an allergic reaction could also either be antibody or cell mediated. This type of allergic reactions occurs in all age groups and damages several different organs, having a significant impact on the emotional and social health of patients and their families and relatives. Concerning introductory comments introduced above, the authors of the present review attempted to collect and provide the latest evidences and information regarding the correlation between expression of eotaxin family members and allergy, in a wider extent, in two important allergic disorders: atopic asthma (AA) and atopic dermatitis (AD). Overall, concerning the most recent articles published within the database in the life sciences literature regarding the fundamental role(s) played by eotaxins in the pathogenesis of AA and AD, the authors of the current article propose that eotaxins (CCL11, CCL24, and CCL26) play key role(s) during symptomatic inflammatory responses raised in response to allergic crisis of these two clinical states.

18β-Glycyrrhetinic acid, the major bioactive component of Glycyrrhizae Radix, attenuates airway inflammation by modulating Th2 cytokines, GATA-3, STAT6, and Foxp3 transcription factors in an asthmatic mouse model.

PubMed

Kim, Seung-Hyung; Hong, Jung-Hee; Lee, Ji-Eun; Lee, Young-Cheol

2017-06-01

18β-Glycyrrhetinic acid (18Gly), the major bioactive component of Glycyrrhizae Radix, possesses anti-ulcerative, anti-inflammatory, and other pharmacological properties. Although 18Gly is associated with immunoregulatory functions of allergic diseases, the pathophysiological mechanisms of 18Gly action in allergic inflammatory lung disease have not been examined. Moreover, there are no in vivo studies on the anti-asthmatic effects of 18Gly in allergic asthma. We investigated its effect and mechanism of action in airway inflammation in a BALB/c mouse model of allergic asthma. Interestingly, 18Gly strongly suppressed airway hyperresponsiveness, accumulation of inflammatory cells, and levels of T helper type 2 (Th2) cytokines (interleukin (IL)-5 and IL-13) in bronchoalveolar lavage fluid (BALF). It also attenuated lung IL-5, IL-13, and IL-4 expression, but it upregulated peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression in lungs. Moreover, it exerted immunomodulatory effects by suppressing Th2 cytokines (IL-5, IL-13) production through upregulation of forkhead box p3 (Foxp3), and downregulation of signal transducer and activator of transcription (STAT6), GATA-binding protein 3 (GATA-3), and retinoic acid-related orphan receptor γ t (RORγt) expression. These results suggest that the anti-asthmatic activity of 18Gly may occur by the suppression of IL-5, IL-13, and OVA-specific Immunoglobulin E (IgE) production through inhibition of the RORγt, STAT6, GATA-3 pathways and upregulation of the Foxp3 transcription pathway. Also, 18Gly treatment was protective against the oxidative stress by inducing significant decrease of reactive oxygen species (ROS) generation in MH-S alveolar macrophage cells. Our results suggest that 18Gly can improve allergic asthma and can be a novel therapeutic component for the treatment of allergic asthma. Copyright © 2017 Elsevier B.V. All rights reserved.

Secretoglobin Superfamily Protein SCGB3A2 Alleviates House Dust Mite-Induced Allergic Airway Inflammation in Mice.

PubMed

Yoneda, Mitsuhiro; Xu, Lei; Kajiyama, Hiroaki; Kawabe, Shuko; Paiz, Jorge; Ward, Jerrold M; Kimura, Shioko

2016-01-01

Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein. Scgb3a2-null (Scgb3a2-/-) mice were subjected to nasal inhalation of Dermatophagoides pteronyssinus extract for 5 days/week for 5 consecutive weeks; control mice received nasal inhalation of saline as a comparator. Airway inflammation was assessed by histological analysis, the number of inflammatory cells and various Th2-type cytokine levels in the lungs and bronchoalveolar lavage fluids by qRT-PCR and ELISA, respectively. Exacerbated inflammation was found in the airway of Scgb3a2-/- mice subjected to house dust mite (HDM)-induced allergic airway inflammation compared with saline-treated control groups. All the inflammation end points were increased in the Scgb3a2-/- mice. The Ccr4 and Ccl17 mRNA levels were higher in HDM-treated lungs of Scgb3a2-/- mice than wild-type mice or saline-treated Scgb3a2-/- mice, whereas no changes were observed for Ccr3 and Ccl11 mRNA levels. These results demonstrate that SCGB3A2 has an anti-inflammatory activity in the HDM-induced allergic airway inflammation model, in which SCGB3A2 may modulate the CCR4-CCL17 pathway. SCGB3A2 may provide a useful tool to treat allergic airway inflammation, and further studies on the levels and function of SCGB3A2 in asthmatic patients are warranted. © 2016 S. Karger AG, Basel.

Regulation of ocular surface inflammation by prostaglandin E receptor subtype EP3.

PubMed

Ueta, Mayumi

2010-11-01

We first investigated whether the prostaglandin (PG) E2-PGE receptor subtype EP3 axis regulates the development of murine experimental allergic conjunctivitis because it has been reported that this pathway negatively regulates allergic reactions in a murine allergic asthma model. We observed that EP3 is constitutively expressed in mice conjunctival epithelium. EP3 knockout mice demonstrated significantly increased eosinophil infiltration in conjunctiva after ragweed challenge compared with wild-type mice. Consistently, significantly higher expression of eotaxin-1 messenger RNA was observed in Ptger3-/- mice. Conversely, treatment of wild-type mice with an EP3-selective agonist significantly decreased eosinophil infiltration, which was blunted in Ptger3-/- mice. Expression of cyclooxygenase-2 and PGE synthases was upregulated and PGE2 content increased in the eyelids after ragweed challenge. These data suggest that PGE2 acts on EP3 in the conjunctival epithelium and downregulates the progression of experimental allergic conjunctivitis. We next examined and compared the expression of EP3 in human conjunctival epithelium in various ocular surface diseases. Human conjunctival epithelium expressed EP3-specific messenger RNA and EP3 protein. Although we could clearly find positive signals in the conjunctival epithelium from patients with noninflammatory ocular surface diseases such as conjunctivochalasis and pterygium, we could not find positive signals in that from those with inflammatory disorders such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid. Likewise, expression of the PGE receptor subtype EP4 was clearly found in the conjunctival epithelium from patients with conjunctivochalasis and pterygium but not from patients with Stevens-Johnson syndrome and ocular cicatricial pemphigoid.

Exploration of the effect of probiotics supplementation on intestinal microbiota of food allergic mice

PubMed Central

Yang, Bo; Xiao, Liang; Liu, Sheng; Liu, Xiaoyu; Luo, Yan; Ji, Qiongmei; Yang, Pingchang; Liu, Zhigang

2017-01-01

Environmental factor-induced alterations in intestinal microbiota have been demonstrated to be associated with increasing prevalence of food allergy. However, it is not clear to what extent oral administration of probiotics can affect gut microbiota composition, thus inhibiting food allergy development. Using ovalbumin (OVA)-sensitized murine model, it was demonstrated that probiotics ameliorated allergic symptoms, including reducing OVA specific-IgE, and -IgG1 levels in the serum, Th2 cytokines release in spleen, and occurrence of diarrhea. Moreover, 16S rRNA analysis showed that the probiotics-mediated protection was conferred by an enrichment of Coprococcus and Rikenella. The present study supports the theory that probiotics can treat food allergy by modulating specific genera of the gut microbiota. PMID:28337267

Transfer of myelin-specific cells deviated in vitro towards IL-4 production ameliorates ongoing experimental allergic neuritis

PubMed Central

Ekerfelt, C; Dahle, C; Weissert, R; Kvarnström, M; Olsson, T; Ernerudh, J

2001-01-01

A causal role of IL-4 (Th2) production for recovery in experimental allergic neuritis (EAN) was indicated by experiments where Th1-like autoreactive cell populations, taken from the induction phase of the disease, were deviated to extensive secretion of IL-4 in a selective fashion, by ex vivo stimulation with autoantigen in the presence of IL-4. The deviated cells were adoptively transferred to EAN rats at a time just prior to the onset of clinical signs. This treatment ameliorated EAN compared with sham treatment. This therapeutic approach, with generation of autoreactive IL-4-secreting cells ex vivo followed by subsequent adoptive transfer, may become a new selective treatment of organ-specific autoimmune diseases since, in contrast to previous attempts, it is done in a physiological and technically easy way. PMID:11168007

Effects of Bifidobacterium Breve Feeding Strategy and Delivery Modes on Experimental Allergic Rhinitis Mice.

PubMed

Ren, Jian-jun; Yu, Zhao; Yang, Feng-Ling; Lv, Dan; Hung, Shi; Zhang, Jie; Lin, Ping; Liu, Shi-Xi; Zhang, Nan; Bachert, Claus

2015-01-01

Different delivery modes may affect the susceptibility to allergic diseases. It is still unknown whether early intervention with probiotics would counteract this effect. The effect of different delivery modes on immune status and nasal symptoms was investigated on established allergic rhinitis (AR) mouse model. In addition, the immunoregulatory effects and mechanisms of different feeding manners with Bifidobacterium breve(B. breve) were examined. Live lyophilized B. breve was orally administered to BALB/c mice born via vaginal delivery(VD) or cesarean delivery (CD) for 8 consecutive weeks, after which they were sensitized by ovalbumin(OVA) to establish experimental AR. Nasal symptoms, serum immunoglobulins, cytokines, splenic percentages of CD4(+)CD25(+)Foxp3(+) regulatory T(Treg) cells and nasal eosinophil infiltration were evaluated. Compared with VD mice, mice delivered via CD demonstrated more serious nasal symptoms, higher concentrations of OVA-specific immunoglobulin (Ig) E, more nasal eosinophils and lower percentages of splenic CD4(+)CD25(+)Foxp3(+)Treg cells after establishing experimental AR. These parameters were reversed by administering B. breves hortly after birth. However, the effect of B. breve did not differ between different delivery modes. CD aggravates the nasal symptoms of AR mice compared to VD. This is the first report that oral administration of B. breve shortly after birth can significantly alleviate the symptoms of AR mice born via both deliveries, probably via activation of the regulatory capacity of CD4(+)CD25(+)Foxp3(+)Treg cells.

T cell epitope immunotherapy ameliorates allergic responses in a murine model of shrimp allergy.

PubMed

Wai, C Y Y; Leung, N Y H; Leung, P S C; Chu, K H

2016-03-01

Shellfish allergy is one of the most common food hypersensitivities worldwide but allergen-specific immunotherapy for shellfish allergy is not yet available. We believe that T cell peptide-based immunotherapy holds the potential for modulating allergic responses without IgE cross-linking. We sought to identify the immunodominant T cell epitopes of tropomyosin, the major shrimp allergen of Metapenaeus ensis (Met e 1), and to evaluate their therapeutic effects in a Balb/c mouse model of Met e 1 hypersensitivity. T cell epitopes of Met e 1 were first identified based on the proliferation and cytokine responses of splenocytes isolated from Met e 1-sensitized Balb/c mice upon stimulation by 18 synthetic peptides that span the full-length Met e 1. The immunodominant T cell peptides identified were then fed orally to Met e 1-sensitized Balb/c mice twice a week for four weeks. Allergic responses, serological antibody levels, intestinal histology and systemic and local cytokine profiles were compared between the treated and the untreated groups. Six major Met e 1 T cell epitopes were identified. Mice treated with the T cell epitope peptide mixture demonstrated an amelioration of systemic allergic symptoms and a significant reduction in Th2-associated antibody and cytokine responses. These benefits were accompanied by a shift to a balanced Th1/Th2 response, induction of IgG2a antibodies possessing in vitro and in vivo blocking activities and the induction of regulatory T cell responses. T cell epitope-based oral immunotherapy is effective in reducing allergic responses towards shrimp tropomyosin. This is a novel strategy for clinical management of shellfish allergy and is a model for mechanistic studies of oral immunotherapy. © 2015 John Wiley & Sons Ltd.

Interaction between allergic asthma and atherosclerosis

PubMed Central

Liu, Conglin; Zhang, Jingying; Shi, Guo-Ping

2015-01-01

Prior studies have established an essential role of mast cells in allergic asthma and atherosclerosis. Mast cell deficiency or inactivation protects mice from allergen-induced airway hyper-responsiveness and diet-induced atherosclerosis, suggesting that mast cells share pathologic activities in both diseases. Allergic asthma and atherosclerosis are inflammatory diseases that contain similar sets of elevated numbers of inflammatory cells in addition to mast cells in the airway and arterial wall, such as macrophages, monocytes, T cells, eosinophils, and smooth muscle cells. Emerging evidence from experimental models and human studies points to a potential interaction between the two seemingly unrelated diseases. Patients or mice with allergic asthma have a high risk of developing atherosclerosis or vice versa, despite the fact that asthma is a Th2-oriented disease, whereas Th1 immunity promotes atherosclerosis. In addition to the preferred Th1/Th2 responses that may differentiate the two diseases, mast cells and many other inflammatory cells also contribute to their pathogenesis by much more than just T cell immunity. Here we summarize the different roles of airway and arterial wall inflammatory cells and vascular cells in asthma and atherosclerosis, and propose an interaction between the two diseases, although limited investigations are available to delineate the molecular and cellular mechanisms by which one disease increases the risk of the other. Results from mouse allergic asthma and atherosclerosis models and from human population studies lead to the hypothesis that patients with atherosclerosis may benefit from anti-asthmatic medications, or that the therapeutic regimens targeting atherosclerosis may also alleviate allergic asthma. PMID:26608212

Propofol inhibits NF-κB activation to ameliorate airway inflammation in ovalbumin (OVA)-induced allergic asthma mice.

PubMed

Zhang, Qiong; Wang, Liangrong; Chen, Baihui; Zhuo, Qian; Bao, Caiying; Lin, Lina

2017-10-01

Propofol, one of the most commonly used intravenous anesthetic agents, has been reported to have anti-inflammatory property. However, the anti-allergic inflammation effect of propofol and its underlying molecular mechanisms have not been elucidated. In the present study, we aim to investigate the roles of NF-kB activation in propofol anti-asthma effect on OVA-induced allergic airway inflammation in mice. In a standard experimental asthma model, Balb/c mice were sensitized with ovalbumin, treated with propofol (50,100,150mg/kg) or a vehicle control 1h before OVA challenge. Blood samples, bronchoalveolar lavage fluid (BALF) and lung tissues were harvested after measurement of airway hyperresponsiveness. Results revealed that propofol not only significantly inhibit airway hyperresponsiveness, but also inhibited the production of Th2 cytokines, NO, Ova-specific IgE and eotaxin. Histological studies indicated that propofol significantly attenuated OVA-induced inflammatory cell infiltration in the peribronchial areas and mucus hypersecretion. Meanwhile, our results indicated that propofol was found to inhibit NF-kB activation in OVA-Induced mice. Furthermore, propofol significantly reduced the TNF-α-induced NF-kB activation in A549 cells. In conclusion, our study suggested that propofol effectively reduced allergic airway inflammation by inhibiting NF-kB activation and could thus be used as a therapy for allergic asthma. Copyright © 2017. Published by Elsevier B.V.

Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

PubMed Central

Ricci, Giampaolo; Astolfi, Annalisa; Remondini, Daniel; Cipriani, Francesca; Formica, Serena; Dondi, Arianna; Pession, Andrea

2011-01-01

Background Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach. Methodology/Principal Findings We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. Conclusion/Significance Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population. PMID:21359210

Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow’s Milk Proteins

PubMed Central

Ibañez, Andrés E.; Smaldini, Paola; Coria, Lorena M.; Delpino, María V.; Pacífico, Lucila G. G.; Oliveira, Sergio C.; Risso, Gabriela S.; Pasquevich, Karina A.; Fossati, Carlos Alberto; Giambartolomei, Guillermo H.; Docena, Guillermo H.; Cassataro, Juliana

2013-01-01

The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow’s Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations. PMID:23861971

Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang).

PubMed

Sá-Nunes, Anderson; Rogerio, Alexandre P; Medeiros, Alexandra I; Fabris, Viciany E; Andreu, Gilberto P; Rivera, Dagmar G; Delgado, René; Faccioli, Lúcia H

2006-09-01

The effects of Vimang, an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae), on cell migration in an experimental model of asthma was investigated. In vivo treatment of Toxocara canis-infected BALB/c mice for 18 days with 50 mg/kg Vimang reduced eosinophil migration into the bronchoalveolar space and peritoneal cavity. Also, eosinophil generation in bone marrow and blood eosinophilia were inhibited in infected mice treated with Vimang. This reduction was associated with inhibition of IL-5 production in serum and eotaxin in lung homogenates. In all these cases the effects of Vimang were more selective than those observed with dexamethasone. Moreover, Vimang treatment is not toxic for the animals, as demonstrated by the normal body weight increase during infection. These data confirm the potent anti-inflammatory effect of Vimang and support its potential use as an alternative therapeutic drug to the treatment of eosinophilic disorders including those caused by nematodes and allergic diseases.

The effect of BCG vaccine at birth on the development of atopy or allergic disease in young children.

PubMed

Townley, R G; Barlan, I B; Patino, C; Vichyanond, P; Minervini, M C; Simasathien, T; Nettagul, R; Bahceciler, N N; Basdemir, D; Akkoc, T; Pongprueksa, S; Hopp, R J

2004-03-01

Exposure to infectious diseases may reduce the development of asthma or allergy. In particular, the role of the BCG vaccine in modulating asthma or allergy has been a source of speculation. To study newborns from 3 international sites to evaluate the prospective effect of BCG vaccine on allergic diseases or atopic development. Infants were enrolled from newborn and well-infant clinics in Thailand, Argentina, and Turkey. The standard BCG vaccine for each country was given at birth. Parents who consented to have their infant included in the protocol completed an allergy family questionnaire. Infants underwent a standard purified protein derivative (PPD) test at 9 to 12 months of age, and the reaction size was measured. At the age of 2 years, the children returned to be studied. Allergy skin tests to common allergens appropriate to location and age were performed, and the parents completed the International Study of Allergy and Asthma in Childhood questionnaire. The PPD reaction size was compared with the presence of atopy and allergy questionnaire responses. A total of 1,704 infants were studied. Statistical significance was found between a negative PPD response vs any positive PPD response and the risk of having an allergic history at the age of 2 years in Turkey (relative risk, 2.11; 95% confidence interval, 1.25-3.55; P = .005) and Thailand (relative risk, 2.16; 95% confidence interval, 1.18-3.94; P = .02) but not Argentina (relative risk, 1.09; 95% confidence interval, 0.70-1.68; P = .70). This study further supports the role of infectious agents in modulating asthma and allergy development.

Basophils and allergic inflammation

PubMed Central

Siracusa, Mark C.; Kim, Brian S.; Spergel, Jonathan M.; Artis, David

2013-01-01

Basophils were discovered by Paul Ehrlich in 1879 and represent the least abundant granulocyte population in mammals. The relative rarity of basophils and their phenotypic similarities with mast cells resulted in this cell lineage being historically overlooked, both clinically and experimentally. However, recent studies in humans and murine systems have shown that basophils perform non-redundant effector functions and significantly contribute to the development and progression of TH2 cytokine-mediated inflammation. Although the potential functions of murine and human basophils have provoked some controversy, recent genetic approaches indicate that basophils can migrate into lymphoid tissues and, in some circumstances, cooperate with other immune cells to promote optimal TH2 cytokine responses in vivo. This article provides a brief historical perspective on basophil-related research and discusses recent studies that have identified previously unappreciated molecules and pathways that regulate basophil development, activation and function in the context of allergic inflammation. Further, we highlight the unique effector functions of basophils and discuss their contributions to the development and pathogenesis of allergic inflammation in human disease. Finally, we discuss the therapeutic potential of targeting basophils in preventing or alleviating the development and progression of allergic inflammation. PMID:24075190

Sex-related clinical aspects in insect venom anaphylaxis.

PubMed

Nittner-Marszalska, Marita; Liebhart, Jerzy; Dor-Wojnarowska, Anna

2015-06-01

Experimental studies, epidemiological data, and clinical observations suggest that the gender factor is involved in the development and manifestation of IgE-dependent allergic diseases. We intend to answer the question if sex-related factors may play a role in Hymenoptera venom allergy (HVA). In the majority of recent studies the frequency of HVA symptoms with respect to both LL and SYS reactions is similar for men and women, while proven sensitization to insect venom is less frequent in women. Studies assessing clinical reactivity in HVA indicate that male sex and vespid venom allergy are factors increasing the risk of severe allergic reactions. Regarding the risk of adverse events associated with gender in the course of venom immunotherapy (VIT), the results of two large EAACI multicenter studies are discordant. In the first study, women showed increased risk of VIT adverse events. In the latter, systemic allergic side effects were not associated with gender. Despite theoretical premises and certain clinical observations indicating an important role of estrogens in allergic diseases, their influence on stinging insects' venom hypersensitivity is not unequivocal and remains still open. Further studies on the safety of VIT in females seem to be advisable. © The Author(s) 2015.

Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation.

PubMed

Pastva, Amy M; Mukherjee, Sambuddho; Giamberardino, Charles; Hsia, Bethany; Lo, Bernice; Sempowski, Gregory D; Wright, Jo Rae

2011-03-01

Although many studies have shown that pulmonary surfactant protein (SP)-A functions in innate immunity, fewer studies have addressed its role in adaptive immunity and allergic hypersensitivity. We hypothesized that SP-A modulates the phenotype and prevalence of dendritic cells (DCs) and CD4(+) T cells to inhibit Th2-associated inflammatory indices associated with allergen-induced inflammation. In an OVA model of allergic hypersensitivity, SP-A(-/-) mice had greater eosinophilia, Th2-associated cytokine levels, and IgE levels compared with wild-type counterparts. Although both OVA-exposed groups had similar proportions of CD86(+) DCs and Foxp3(+) T regulatory cells, the SP-A(-/-) mice had elevated proportions of CD4(+) activated and effector memory T cells in their lungs compared with wild-type mice. Ex vivo recall stimulation of CD4(+) T cell pools demonstrated that cells from the SP-A(-/-) OVA mice had the greatest proliferative and IL-4-producing capacity, and this capability was attenuated with exogenous SP-A treatment. Additionally, tracking proliferation in vivo demonstrated that CD4(+) activated and effector memory T cells expanded to the greatest extent in the lungs of SP-A(-/-) OVA mice. Taken together, our data suggested that SP-A influences the prevalence, types, and functions of CD4(+) T cells in the lungs during allergic inflammation and that SP deficiency modifies the severity of inflammation in allergic hypersensitivity conditions like asthma.

Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

PubMed

Norris, C R; Byerly, J R; Decile, K C; Berghaus, R D; Walby, W F; Schelegle, E S; Hyde, D M; Gershwin, L J

2003-12-15

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

Phenolic compounds from red wine and coffee are associated with specific intestinal microorganisms in allergic subjects.

PubMed

Cuervo, Adriana; Hevia, Arancha; López, Patricia; Suárez, Ana; Diaz, Carmen; Sánchez, Borja; Margolles, Abelardo; González, Sonia

2016-01-01

The dietary modulation of gut microbiota, suggested to be involved in allergy processes, has recently attracted much interest. While several studies have addressed the use of fibres to modify intestinal microbial populations, information about other components, such as phenolic compounds, is scarce. The aim of this work was to identify the dietary components able to influence the microbiota in 23 subjects suffering from rhinitis and allergic asthma, and 22 age- and sex-matched controls. The food intake was recorded by means of an annual food frequency questionnaire. Dietary fibre tables were obtained from Marlett et al., and the Phenol-Explorer database was used to assess the phenolic compound intake. The quantification of microbial groups was performed using an Ion Torrent 16S rRNA gene-based analysis. The results showed a direct association between the intake of red wine, a source of stilbenes, and the relative abundance of Bacteroides, and between the intake of coffee, rich in phenolic acids, and the abundance of Clostridium, Lactococcus and Lactobacillus genera. Despite epidemiological analyses not establishing causality, these results support the association between polyphenol-rich beverages and faecal microbiota in allergic patients.

Changes in gene expression in chronic allergy mouse model exposed to natural environmental PM2.5-rich ambient air pollution.

PubMed

Ouyang, Yuhui; Xu, Zhaojun; Fan, Erzhong; Li, Ying; Miyake, Kunio; Xu, Xianyan; Zhang, Luo

2018-04-20

Particulate matter (PM) air pollution has been associated with an increase in the incidence of chronic allergic diseases; however, the mechanisms underlying the effect of exposure to natural ambient air pollution in chronic allergic diseases have not been fully elucidated. In the present study, we aimed to investigate the cellular responses induced by exposure to natural ambient air pollution, employing a mouse model of chronic allergy. The results indicated that exposure to ambient air pollution significantly increased the number of eosinophils in the nasal mucosa. The modulation of gene expression profile identified a set of regulated genes, and the Triggering Receptor Expressed on Myeloid cells1(TREM1) signaling canonical pathway was increased after exposure to ambient air pollution. In vitro, PM2.5 increased Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) and nuclear factor (NF)-κB signaling pathway activation in A549 and HEK293 cell cultures. These results suggest a novel mechanism by which, PM2.5 in ambient air pollution may stimulate the innate immune system through the PM2.5-Nod1-NF-κB axis in chronic allergic disease.

Epigenetic regulation in allergic diseases and related studies

PubMed Central

Kuo, Chang-Hung; Hsieh, Chong-Chao; Lee, Min-Sheng; Chang, Kai-Ting; Kuo, Hsuan-Fu

2014-01-01

Asthma, a chronic inflammatory disorder of the airway, has features of both heritability as well as environmental influences which can be introduced in utero exposures and modified through aging, and the features may attribute to epigenetic regulation. Epigenetic regulation explains the association between early prenatal maternal smoking and later asthma-related outcomes. Epigenetic marks (DNA methylation, modifications of histone tails or noncoding RNAs) work with other components of the cellular regulatory machinery to control the levels of expressed genes, and several allergy- and asthma-related genes have been found to be susceptible to epigenetic regulation, including genes important to T-effector pathways (IFN-γ, interleukin [IL] 4, IL-13, IL-17) and T-regulatory pathways (FoxP3). Therefore, the mechanism by which epigenetic regulation contributes to allergic diseases is a critical issue. In the past most published experimental work, with few exceptions, has only comprised small observational studies and models in cell systems and animals. However, very recently exciting and elegant experimental studies and novel translational research works were published with new and advanced technologies investigating epigenetic mark on a genomic scale and comprehensive approaches to data analysis. Interestingly, a potential link between exposure to environmental pollutants and the occurrence of allergic diseases is revealed recently, particular in developed and industrialized countries, and endocrine disrupting chemicals (EDCs) as environmental hormone may play a key role. This review addresses the important question of how EDCs (nonylphenol, 4 octylphenol, and phthalates) influences on asthma-related gene expression via epigenetic regulation in immune cells, and how anti-asthmatic agents prohibit expression of inflammatory genes via epigenetic modification. The discovery and validation of epigenetic biomarkers linking exposure to allergic diseases might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies. PMID:24527405

Dysregulation of metabolic pathways in a mouse model of allergic asthma.

PubMed

Quinn, K D; Schedel, M; Nkrumah-Elie, Y; Joetham, A; Armstrong, M; Cruickshank-Quinn, C; Reisdorph, R; Gelfand, E W; Reisdorph, N

2017-09-01

Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function. In this experimental model of allergic asthma, matched bronchoalveolar lavage (BAL) fluid and plasma were collected from three groups of C57BL6 mice (control vs sensitized and/or challenged with ovalbumin, n=3-5/group) 6 hour, 24 hour, and 48 hour after the last challenge. Samples were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Airway hyper-responsiveness (AHR) measurements and differential cell counts were performed. In total, 398 and 368 dysregulated metabolites in the BAL fluid and plasma of sensitized and challenged mice were identified, respectively. These belonged to four, interconnected pathways relevant to asthma pathogenesis: sphingolipid metabolism (P=6.6×10 -5 ), arginine and proline metabolism (P=1.12×10 -7 ), glycerophospholipid metabolism (P=1.3×10 -10 ), and the neurotrophin signaling pathway (P=7.0×10 -6 ). Furthermore, within the arginine and proline metabolism pathway, a positive correlation between urea-1-carboxylate and AHR was observed in plasma metabolites, while ornithine revealed a reciprocal effect. In addition, agmatine positively correlated with lung eosinophilia. These findings point to potential targets and pathways that may be central to asthma pathogenesis and can serve as novel therapeutic targets. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Vitamin E and mast cells.

PubMed

Zingg, Jean-Marc

2007-01-01

Mast cells play an important role in the immune system by interacting with B and T cells and by releasing several mediators involved in activating other cells. Hyperreactivity of mast cells and their uncontrolled accumulation in tissues lead to increased release of inflammatory mediators contributing to the pathogenesis of several diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and allergic disorders such as asthma and allergic rhinitis. Interference with mast cell proliferation, survival, degranulation, and migration by synthetic or natural compounds may represent a preventive strategy for the management of these diseases. Natural vitamin E covers a group of eight analogues-the alpha-, beta-, gamma-, and delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols, but only alpha-tocopherol is efficiently retained by the liver and distributed to peripheral tissues. Mast cells preferentially locate in the proximity of tissues that interface with the external environment (the epithelial surface of the skin, the gastrointestinal mucosa, and the respiratory system), what may render them accessible to treatments with inefficiently retained natural vitamin E analogues and synthetic derivatives. In addition to scavenging free radicals, the natural vitamin E analogues differently modulate signal transduction and gene expression in several cell lines; in mast cells, protein kinase C, protein phosphatase 2A, and protein kinase B are affected by vitamin E, leading to the modulation of proliferation, apoptosis, secretion, and migration. In this chapter, the possibility that vitamin E can prevent diseases with mast cells involvement by modulating signal transduction and gene expression is evaluated.

CD24(hi)CD27(+) B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide.

PubMed

van der Vlugt, L E P M; Mlejnek, E; Ozir-Fazalalikhan, A; Janssen Bonas, M; Dijksman, T R; Labuda, L A; Schot, R; Guigas, B; Möller, G M; Hiemstra, P S; Yazdanbakhsh, M; Smits, H H

2014-04-01

Regulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma. In this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated. Isolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4(+) T cells and house dust mite allergen DerP1. Lower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24(hi)CD27(+) B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4(+) T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24(hi)CD27(+) B cells are responsible for the induction of IL-10(+) CD4(+) T cells. Taken together, these data indicate that CD24(hi)CD27(+) B cells from allergic asthma patients produce less IL-10 in response to LPS leading to a weaker IL-10 induction in T cells in response to DerP1, which may play a role in allergic asthma. © 2013 John Wiley & Sons Ltd.

Different implications of paternal and maternal atopy for perinatal IgE production and asthma development.

PubMed

Wu, Chih-Chiang; Chen, Rong-Fu; Kuo, Ho-Chang

2012-01-01

Asthma is a hereditary disease associated with IgE-mediated reaction. Whether maternal atopy and paternal atopy have different impacts on perinatal IgE production and asthma development remains unclear. This paper reviews and summarizes the effects of maternal and paternal atopy on the developmental aspects of IgE production and asthma. Maternal atopy affects both pre- and postnatal IgE production, whereas paternal atopy mainly affects the latter. Maternally transmitted genes GSTP1 and FceRI-beta are associated with lung function and allergic sensitization, respectively. In IgE production and asthma development, the maternal influence on gene-environment interaction is greater than paternal influence. Maternal, paternal, and/or postnatal environmental modulation of allergic responses have been linked to epigenetic mechanisms, which may be good targets for early prevention of asthma.

Different Implications of Paternal and Maternal Atopy for Perinatal IgE Production and Asthma Development

PubMed Central

Wu, Chih-Chiang; Chen, Rong-Fu; Kuo, Ho-Chang

2012-01-01

Asthma is a hereditary disease associated with IgE-mediated reaction. Whether maternal atopy and paternal atopy have different impacts on perinatal IgE production and asthma development remains unclear. This paper reviews and summarizes the effects of maternal and paternal atopy on the developmental aspects of IgE production and asthma. Maternal atopy affects both pre- and postnatal IgE production, whereas paternal atopy mainly affects the latter. Maternally transmitted genes GSTP1 and FceRI-beta are associated with lung function and allergic sensitization, respectively. In IgE production and asthma development, the maternal influence on gene-environment interaction is greater than paternal influence. Maternal, paternal, and/or postnatal environmental modulation of allergic responses have been linked to epigenetic mechanisms, which may be good targets for early prevention of asthma. PMID:22272211

Differential expression of 11β-hydroxysteroid dehydrogenase type 1 and 2 in mild and moderate/severe persistent allergic nasal mucosa and regulation of their expression by Th2 cytokines: asthma and rhinitis.

PubMed

Jun, Y J; Park, S J; Hwang, J W; Kim, T H; Jung, K J; Jung, J Y; Hwang, G H; Lee, S H; Lee, S H

2014-02-01

Glucocorticoids are used to treat allergic rhinitis, but the mechanisms by which they induce disease remission are unclear. 11β-hydroxysteroid dehydrogenase (11β-HSD) is a tissue-specific regulator of glucocorticoid responses, inducing the interconversion of inactive and active glucocorticoids. We analysed the expression and distribution patterns of 11β-HSD1, 11β-HSD2, and steroidogenic enzymes in normal and allergic nasal mucosa, and cytokine-driven regulation of their expression. The production levels of cortisol in normal, allergic nasal mucosa and in cultured epithelial cells stimulated with cytokines were also determined. The expression levels of 11β-HSD1, 11β-HSD2, steroidogenic enzymes (CYP11B1, CYP11A1), and cortisol in normal, mild, and moderate/severe persistent allergic nasal mucosa were assessed by real-time PCR, Western blot, immunohistochemistry, and ELISA. The expression levels of 11β-HSD1, 11β-HSD2, CYP11B1, CYP11A1, and cortisol were also determined in cultured nasal epithelial cell treated with IL-4, IL-5, IL-13, IL-17A, and IFN-γ. Conversion ratio of cortisone to cortisol was evaluated using siRNA technique, 11β-HSD1 inhibitor, and the measurement of 11β-HSD1 activity. The expression levels of 11β-HSD1, CYP11B1, and cortisol were up-regulated in mild and moderate/severe persistent allergic nasal mucosa. By contrast, 11β-HSD2 expression was decreased in allergic nasal mucosa. In cultured epithelial cells treated with IL-4, IL-5, IL-13, and IL-17A, 11β-HSD1 expression and activity increased in parallel with the expression levels of CYP11B1 and cortisol, but the production of 11β-HSD2 decreased. CYP11A1 expression level was not changed in allergic nasal mucosa or in response to stimulation with cytokines. SiRNA technique or the measurement of 11β-HSD1 activity showed that nasal epithelium activates cortisone to cortisol in a 11β-HSD-dependent manner. These results indicate that the localized anti-inflammatory effects of glucocorticoids are regulated by inflammatory cytokines, which can modulate the expression of 11β-HSD1, 11β-HSD2, and CYP11B1, and by the intracellular concentrations of bioactive glucocorticoids. © 2013 John Wiley & Sons Ltd.

Shikonin inhibits maturation of bone marrow-derived dendritic cells and suppresses allergic airway inflammation in a murine model of asthma

PubMed Central

Lee, Chen-Chen; Wang, Chien-Neng; Lai, Yu-Ting; Kang, Jaw-Jou; Liao, Jiunn-Wang; Chiang, Bor-Luen; Chen, Hui-Chen; Cheng, Yu-Wen

2010-01-01

BACKGROUND AND PURPOSE Shikonin exhibits a wide range of anti-inflammatory actions. Here, we assessed its effects on maturation of murine bone marrow-derived dendritic cells (BM-DCs) and on allergic reactions in a murine model of asthma. EXPERIMENTAL APPROACH Cultured murine BM-DCs were used to investigate the effects of shikonin on expression of cell surface markers and their stimulation of T-cell proliferation and cytokine production. The therapeutic potential of shikonin was evaluated in a model of allergic airway disease. KEY RESULTS Shikonin dose-dependently inhibited expression of major histocompatibility complex class II, CD80, CD86, CCR7 and OX40L on BM-DCs, induced by a mixture of ovalbumin (OVA; 100 µg·mL−1) and thymic stromal lymphopoietin (TSLP; 20 ng·mL−1). Shikonin-treated BM-DCs were poor stimulators of CD4+ T lymphocyte and induced lower levels of interleukin (IL)-4, IL-5, IL-13 and tumour necrosis factor (TNF)-α release by responding T-cells. After intratracheal instillation of shikonin in OVA-immunized mice, OVA challenge induced lower IL-4, IL-5, IL-13, TNF-α and eotaxin release in bronchial alveolar lavage fluid, lower IL-4 and IL-5 production in lung cells and mediastinal lymph node cells and attenuated OVA-induced lung eosinophilia and airway hyperresponsiveness. CONCLUSION AND IMPLICATIONS Shikonin effectively suppressed OVA + TSLP-induced BM-DC maturation in vitro and inhibited allergic inflammation and airway hyperresponsiveness in a murine model of asthma, showing good potential as a treatment for allergic asthma. Also, our model provides a novel platform for screening drugs for allergic diseases. PMID:20735407

Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma.

PubMed

Kim, Dong Eon; Lee, Yonghyun; Kim, MinGyo; Lee, Soyoung; Jon, Sangyong; Lee, Seung-Hyo

2017-09-01

Although asthma, a chronic inflammatory airway disease, is relatively well-managed by inhaled corticosteroids, the side effects associated with the long-term use of these agents precipitate the need for alternative therapeutic options based on differing modes of action. Bilirubin, a potent endogenous antioxidant, and anti-inflammatory molecule have been shown to ameliorate asthmatic symptoms; however, its clinical translation has been limited owing to its water insolubility and associated potential toxicity. Here we report the first application of bilirubin-based nanoparticles (BRNPs) as a nanomedicine for the treatment of allergic lung inflammatory disease. BRNPs were prepared directly from self-assembly of PEGylated bilirubin in aqueous solution and had a hydrodynamic diameter of ∼100 nm. Because allergen-specific type 2 T-helper (Th2) cells play a key role in the pathogenesis and progression of allergic asthma, the effects of BRNPs on Th2 immune responses were investigated both in vivo and in vitro. BRNPs after intravenous injection (i.v.) showed much higher serum concentration and a longer circulation time of bilirubin than the intraperitoneal injection (i.p.) of BRNPs or unconjugated bilirubin (UCB). The anti-asthmatic effects of BRNPs were assessed in a mouse model of allergen-induced asthma. Compared with UCB, treatment with BRNPs suppressed the symptoms of experimental allergic asthma and dramatically ameliorated Th2-related allergic lung inflammation. Consistent with these results, BRNPs caused a reduction of Th2 cell populations and the expression of related cytokines by antibody-stimulated CD4 + T cells in vitro. Therefore, our results establish BRNPs as an important immunomodulatory agent that may be useful as a therapeutic for allergic lung inflammatory disease and other immune-mediated disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Volatile Organic Compounds Enhance Allergic Airway Inflammation in an Experimental Mouse Model

PubMed Central

Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C.; Lehmann, Irina; Polte, Tobias

2012-01-01

Background Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. Methods To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Results Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Conclusions Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases. PMID:22802943

Volatile organic compounds enhance allergic airway inflammation in an experimental mouse model.

PubMed

Bönisch, Ulrike; Böhme, Alexander; Kohajda, Tibor; Mögel, Iljana; Schütze, Nicole; von Bergen, Martin; Simon, Jan C; Lehmann, Irina; Polte, Tobias

2012-01-01

Epidemiological studies suggest an association between exposure to volatile organic compounds (VOCs) and adverse allergic and respiratory symptoms. However, whether VOCs exhibit a causal role as adjuvants in asthma development remains unclear. To investigate the effect of VOC exposure on the development of allergic airway inflammation Balb/c mice were exposed to VOCs emitted by new polyvinylchloride (PVC) flooring, sensitized with ovalbumin (OVA) and characterized in acute and chronic murine asthma models. Furthermore, prevalent evaporated VOCs were analyzed and mice were exposed to selected single VOCs. Exposure of mice to PVC flooring increased eosinophilic lung inflammation and OVA-specific IgE serum levels compared to un-exposed control mice. The increased inflammation was associated with elevated levels of Th2-cytokines. Long-term exposure to PVC flooring exacerbated chronic airway inflammation. VOCs with the highest concentrations emitted by new PVC flooring were N-methyl-2-pyrrolidone (NMP) and 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB). Exposure to NMP or TXIB also increased the allergic immune response in OVA-sensitized mice. In vitro or in vivo exposure to NMP or TXIB reduced IL-12 production in maturing dendritic cells (DCs) and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. At higher concentrations both VOCs induced oxidative stress demonstrated by increased isoprostane and glutathione-S-transferase-pi1 protein levels in the lung of non-sensitized mice. Treatment of PVC flooring-exposed mice with N-acetylcysteine prevented the VOC-induced increase of airway inflammation. Our results demonstrate that exposure to VOCs may increase the allergic immune response by interfering with DC function and by inducing oxidative stress and has therefore to be considerate as risk factor for the development of allergic diseases.

Master switches of T-cell activation and differentiation.

PubMed

Beier, K C; Kallinich, T; Hamelmann, E

2007-04-01

T-cells play a central role in allergic airway diseases such as bronchial asthma. The imbalance between allergen-specific pro-inflammatory and pro-allergic T-cell responses on one hand and regulatory or suppressive T-cell responses on the other may best explain the development of unwanted immune responses against environmental allergens, which lead to immunoglobulin E production and airway inflammation. A key role in the fine tuning of any T-cell response is provided by the engagement of so-called co-stimulatory molecules that are required for the full activation of T-cells and the recognition of antigens via the antigen-specific T-cell receptor. Many of these co-stimulatory molecules have been identified only recently, leading to a fundamental change in the overall understanding of T-cell regulation. Due to their pivotal impact on T-cell differentiation and control, co-stimulatory molecules are promising targets for therapeutic intervention in T-cell-regulated or -mediated immune disorders, including allergic diseases and asthma. In the present article, an attempt is made to summarise the current knowledge on the basic concept of co-stimulation, the presently known co-stimulatory molecules and their various functions on T-cell activation or suppression. The mini-series will be completed by two more articles describing the recent experimental studies and preliminary clinical findings regarding the role of co-stimulatory molecules in allergic disorders and bronchial asthma, and a discussion regarding the feasibility of co-stimulatory molecules as potential targets for the treatment of allergic airway disease. Although it is too early for any clinical implication or utilisation at this moment, the authors are convinced that a better understanding of co-stimulation in the context of allergic asthma will finally provide novel and promising approaches for treatment and prevention.

Evaluation of the Effects of Sativex (THC BDS: CBD BDS) on Inhibition of Spasticity in a Chronic Relapsing Experimental Allergic Autoimmune Encephalomyelitis: A Model of Multiple Sclerosis

PubMed Central

Hilliard, A.; Stott, C.; Wright, S.; Guy, G.; Pryce, G.; Al-Izki, S.; Bolton, C.; Giovannoni, G.

2012-01-01

This study investigated the antispasticity potential of Sativex in mice. Chronic relapsing experimental allergic encephalomyelitis was induced in adult ABH mice resulting in hind limb spasticity development. Vehicle, Sativex, and baclofen (as a positive control) were injected intravenously and the “stiffness” of limbs assessed by the resistance force against hind limb flexion. Vehicle alone caused no significant change in spasticity. Baclofen (5 mg/kg) induced approximately a 40% peak reduction in spasticity. Sativex dose dependently reduced spasticity; 5 mg/kg THC + 5 mg/kg CBD induced approximately a 20% peak reduction; 10 mg/kg THC + 10 mg/kg CBD produced approximately a 40% peak reduction in spasticity. Sativex has the potential to reduce spasticity in an experimental mouse model of multiple sclerosis (MS). Baclofen reduced spasticity and served as a positive control. Sativex (10 mg/kg) was just as effective as baclofen, providing supportive evidence for Sativex use in the treatment of spasticity in MS. PMID:22928118

Developments in the field of allergy in 2011 through the eyes of Clinical and Experimental Allergy.

PubMed

Arshad, S H; Dharmage, S C; Ferreira, F; Fixman, E D; Gadermaier, G; Hauser, M; Sampson, A P; Teran, L M; Wallner, M; Wardlaw, A J

2012-12-01

As in previous years, we felt it would be of value to our readership to summarize the new information provided by the authors who have published in Clinical and Experimental Allergy in 2011 and set this in the context of recent advances in our understanding of the pathogenesis and management of allergic disease in all its many manifestations. In 2011, about 210 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, guidelines, letters, book reviews and of course at the heart of the journal, papers containing original data. As before, this review is divided into sections based on the way the journal is structured, although this year we have grouped together all the papers dealing with mechanisms of allergic disease, whether they involve patients (clinical mechanisms), pure in vitro studies (basic mechanisms) or animal models (experimental models), as we felt this was a more coherent way to deal with the subject. In the field of asthma and rhinitis, the relationship between airway inflammation and airway dysfunction was of perennial interest to investigators, as were phenotypes and biomarkers. Aspirin hypersensitivity appeared in studies in several papers and there was new interest in asthma in the elderly. The mechanisms involved in allergic disease describe advances in our understanding of T cell responses, the relationship between inflammation and disease, mast cell and basophil activation, steroid resistance and novel therapies. In the section dealing with epidemiology, studies seeking to identify risk factors for allergic disease including vitamin D are prominent, as once again are studies investigating gene-environment interactions. The clinical allergy section focuses on drug allergy, food allergy and immunotherapy. The area of oral immunotherapy for food allergy is well covered and we were grateful to Stephen Durham for guest editing an outstanding special issue on immunotherapy in the centenary year of Leonard Noon's pioneering work. Lastly, in the field of allergens, the interest in component-resolved diagnosis continues to grow and there are also articles describing important novel cultivars and the effect of food processing on the allergenic properties of foods. Another terrific year, full of important and high-quality work,which the journal has been proud to bring to the allergy community. © 2012 Blackwell Publishing Ltd.

Probiotics and down-regulation of the allergic response.

PubMed

Kalliomäki, Marko A; Isolauri, Erika

2004-11-01

The first clinical trials with probiotics, especially in the treatment of atopic eczema, have yielded encouraging results. Experimental studies have found that probiotics exert strain-specific effects in the intestinal lumen and on epithelial cells and immune cells with anti-allergic potential. These effects include enhancement in antigen degradation and gut barrier function and induction of regulatory and proinflammatory immune responses, the latter of which occurs more likely beyond the intestinal epithelium. Future studies should address more accurately how these and other possible mechanisms operate in the complex gastrointestinal macroenvironment in vivo and how these mechanisms are related to the clinical effects in a dose-dependent manner.

Oleanolic acid acetate inhibits atopic dermatitis and allergic contact dermatitis in a murine model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Jin Kyeong; Oh, Hyun-Mee; Lee, Soyoung

2013-05-15

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are common allergic and inflammatory skin diseases caused by a combination of eczema, scratching, pruritus, and cutaneous sensitization with allergens. This paper examines whether oleanolic acid acetate (OAA) modulates AD and ACD symptoms by using an existing AD model based on the repeated local exposure of mite extract (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene to the ears of BALB/c mice. In addition, the paper uses a 2,4-dinitrofluorobenzene-sensitized local lymph node assay (LLNA) for the ACD model. The oral administration of OAA over a four-week period attenuated AD symptoms in terms of decreasedmore » skin lesions, epidermal thickness, the infiltration of immune cells (CD4{sup +} cells, eosinophils, and mast cells), and serum IgE, IgG2a, and histamine levels. The gene expression of Th1, Th2, Th17, and Th22 cytokines was reduced by OAA in the lymph node and ear tissue, and the LLNA verified that OAA suppressed ACD. The oral administration of OAA over a three-day period attenuated ACD symptoms in terms of ear thickness, lymphocyte proliferation, and serum IgG2a levels. The gene expression of Th1, Th2, and Th17 cytokines was reduced by OAA in the thymus and ear tissue. Finally, to define the underlying mechanism, this paper uses a TNF-α/IFN-γ-activated human keratinocyte (HaCaT) model. OAA inhibited the expression of cytokines and chemokines through the downregulation of NF-κB and MAPKs in HaCaT cells. Taken together, the results indicate that OAA inhibited AD and ACD symptoms, suggesting that OAA may be effective in treating allergic skin disorders. - Highlights: • OAA reduced both acute and chronic AD symptoms. • OAA had a controlling effect on the immune reaction for ACD. • The effect of OAA on allergic skin disorders was comparable to the cyclosporine A. • OAA might be a candidate for the treatment of allergic skin disorders.« less

Developments in the field of allergy in 2010 through the eyes of Clinical and Experimental Allergy.

PubMed

Katelaris, C H; Linneberg, A; Magnan, A; Thomas, W R; Wardlaw, A J; Wark, P

2011-12-01

In 2010 over 200 articles were published in Clinical and Experimental Allergy including editorials, reviews, opinion articles, letters, book reviews and of course at the heart of the journal, papers containing original data which have moved the field of allergy forward on a number of fronts. For the third year running the editors felt it would be of value to summarize the key messages contained in these papers as a snapshot of where the cutting edge of research into allergic disease is leading. We have broadly followed the sections of the journal, although this year the mechanistic articles are grouped together and the studies involving experimental models of disease are discussed throughout the paper. In the field of asthma and rhinitis phenotypes and biomarkers continue to a major pre-occupation of our authors. There is continued interest in mechanisms of inflammation and disordered lung function with the mouse model of asthma continuing to offer new insights. There is also a steady flow of papers investigating new therapies, including those derived from plants and herbs, although many are mechanistic with too few high quality clinical trials. The mechanisms involved in allergic disease are well covered with many strong papers using clinical material to ask relevant questions. Pro-pre and snybiotics continue to be of major interest to our authors and this remains a controversial and complicated field. The discipline of epidemiology has retained its interest in risk factors for the development of allergic disease with a view to refining and debating the reasons for the allergy epidemic. There is continued interest in the relationship between helminthic disease and allergy with a new twist in 2010 involving studies using infection with helminths as a potential treatment. The genetics of allergic disease continues to be very productive, although the field has moved on from only investigating single nucleotide polymorphisms of candidate genes to Genome Wide Association Studies and an increasing and welcome emphasis on gene-environment interactions. In the field of clinical allergy there is steady flow of papers describing patterns of drug allergy with renewed interest in reactions to contrast media, but food allergy is the major area of interest in this section of the journal. Lastly in the field of allergens there is a growing interest in the role of component resolved diagnosis in improving the diagnosis and management of allergic disease. Another excellent year, full of fascinating and high quality work, which the journal has been proud to bring to the allergy community. © 2011 Blackwell Publishing Ltd.

Topical royal jelly alleviates symptoms of pruritus in a murine model of allergic contact dermatitis.

PubMed

Yamaura, Katsunori; Tomono, Ayana; Suwa, Eriko; Ueno, Koichi

2013-01-01

Royal jelly is widely used as a health tonic, especially in Asia. Royal jelly is commonly used in cosmetics as well as in dietary supplements and beverages. Little is known, however, about the pharmacologic efficacy of topical royal jelly. Therefore, we investigated the antipruritic activity of topical royal jelly on chronic pruritus in experimental allergic contact dermatitis in mice. HAIRLESS MICE (HOS: HR-1), with chronic allergic contact dermatitis induced by 5 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the entire back skin were treated topically with royal jelly (0.01% or 1%) for 5 weeks after sensitization with TNCB. The effects of royal jelly on pruritus and inflammation were evaluated by measurement of scratching behavior and skin inflammation score, respectively. Repeated application of TNCB to the back skin of mice elicited frequent scratching behavior immediately and 24h after challenge. Topical royal jelly (0.01% or 1%) and betamethasone (0.01%) significantly ameliorated this chronic pruritus throughout the experimental period. The level of nerve growth factor mRNA in back skin was increased in the mice with dermatitis and reduced by betamethasone, but not by royal jelly. The inhibitory effect of royal jelly on chronic pruritus may occur through different mechanisms from those of betamethasone. Topical application of royal jelly, as used in cosmetics, might be beneficial for the alleviation of chronic pruritus.

Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma

PubMed Central

Zhang, Yun; Xu, Yun; Liu, Shuwan; Guo, Xiaohong; Cen, Dong; Xu, Jiaqi; Li, Heyuan; Li, Kaijun; Zeng, Chunlai; Lu, Linrong; Zhou, Yiting; Shen, Huahao; Cheng, Hongqiang; Zhang, Xue; Ke, Yuehai

2016-01-01

Asthma is a common allergic disorder involving a complex interplay among multiple genetic and environmental factors. Recent studies identified genetic variants of human GAB1 as a novel asthma susceptibility factor. However, the functions of Gab1 in lung remain largely unexplored. In this study, we first observed an elevation of Gab1 level in peripheral blood mononuclear cells from asthmatic patients during acute exacerbation compared with convalescence. Mice with a selectively disrupted Gab1 in myeloid dendritic cells (mDCs) considerably attenuated allergic inflammation in experimental models of asthma. Further investigations revealed a prominent reduction in CCL19-mediated migration of Gab1-deficient mDCs to draining lymph nodes and subsequent impairment of Th2-driven adaptive activation. Mechanistically, Gab1 is an essential component of the CCL19/CCR7 chemokine axis that regulates mDC migration during asthmatic responses. Together, these findings provide the first evidence for the roles of Gab1 in lung, giving us deeper understanding of asthmatic pathogenesis. PMID:27811945

Can infections prevent or cure allergy and autoimmunity?

PubMed

Kamradt, Thomas

2005-06-01

Extract: In western countries the prevalence and incidence of allergic and autoimmune diseases have been increasing dramatically over the last 50 years. In the last two decades, significant progress has been made towards understanding the genetic basis for susceptibility to autoimmunity or allergy. Genetic factors, however, cannot explain abrupt changes in disease incidence. It is therefore likely that environmental factors, specifically environmental factors that have changed over the last two generations, are critical for the increasing incidence of allergies and autoimmune diseases. Traditionally, autoimmune diseases such as multiple sclerosis (MS), type I diabetes, or rheumatoid arthritis (RA) are believed to have resulted from aberrant immune response to pathogens. In contrast, the "hygiene hypothesis," first postulated some 20 years ago, proposes that a lack of infections, especially during early childhood, predisposes one to the aberrant immune responses against harmless foreign antigens that cause allergic diseases such as rhinitis, atopic dermatitis, and allergic asthma. Several lines of epidemiological, clinical and experimental research point to more complex connections, either protective or pathogenic, between infection, allergy and autoimmunity.

Motor activity as an unbiased variable to assess anaphylaxis in allergic rats.

PubMed

Abril-Gil, Mar; Garcia-Just, Alba; Cambras, Trinitat; Pérez-Cano, Francisco J; Castellote, Cristina; Franch, Àngels; Castell, Margarida

2015-10-01

The release of mediators by mast cells triggers allergic symptoms involving various physiological systems and, in the most severe cases, the development of anaphylactic shock compromising mainly the nervous and cardiovascular systems. We aimed to establish variables to objectively study the anaphylactic response (AR) after an oral challenge in an allergy model. Brown Norway rats were immunized by intraperitoneal injection of ovalbumin with alum and toxin from Bordetella pertussis. Specific immunoglobulin (Ig) E antibodies were developed in immunized animals. Forty days after immunization, the rats were orally challenged with the allergen, and motor activity, body temperature and serum mast cell protease concentration were determined. The anaphylaxis induced a reduction in body temperature and a decrease in the number of animal movements, which was inversely correlated with serum mast cell protease release. In summary, motor activity is a reliable tool for assessing AR and also an unbiased method for screening new anti-allergic drugs. © 2015 by the Society for Experimental Biology and Medicine.

Inhibition of Mast Cell-Mediated Allergic Responses by Arctii Fructus Extracts and Its Main Compound Arctigenin.

PubMed

Kee, Ji-Ye; Hong, Seung-Heon

2017-11-01

The Arctium lappa seeds (Arctii Fructus) and its major active compound, arctigenin (ARC), are known to have anticancer, antiobesity, antiosteoporosis, and anti-inflammatory activities. However, the effect of Arctii Fructus and ARC on mast cell-mediated allergic inflammation and its associated mechanism have not been elucidated. Therefore, we attempted to investigate the antiallergic activity of Arctii Fructus and ARC on mast cells and experimental mouse models. Arctii Fructus water extract (AFW) or ethanol extract (AFE) and ARC reduced the production of histamine and pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-8, and TNF-α in mast cells. AFW, AFE, and ARC inhibited phosphorylation of MAPKs and NF-κB in activated mast cells. Moreover, IgE-mediated passive cutaneous anaphylaxis and compound 48/80-induced anaphylactic shock were suppressed by AFW, AFE, and ARC administration. These results suggest that Arctii Fructus and ARC are potential therapeutic agents against allergic inflammatory diseases.

Promising treatments in development for food allergies.

PubMed

Rancé, Fabienne

2004-11-01

Up to 6% of young children and 2% of adults suffer from food allergy. Among them many have IgE-mediated food allergy, a condition with potentially fatal allergic reactions. The only proven treatment is avoidance of the offending food, which can be identified using standardised allergic tests. However, several studies have addressed possible definite treatment options for food allergy. Immunotherapy, administered orally or by systemic injections, shows promising preliminary results, but these therapeutics are based on studies with insufficient scientific support, or are associated with a high risk of severe side effects. At present, no studies can support pharmacotherapy. However, promising results were recently published with anti-IgE antibodies in a human trial, and various approaches in a mouse model of food allergy (chinese herbal medicine, specific modulation of the T-cell response). Rapidly evolving findings might provide hope for a cure for food allergy in the near future.

Mechanistic impact of outdoor air pollution on asthma and allergic diseases

PubMed Central

Zhang, Qingling; Qiu, Zhiming; Chung, Kian Fan

2015-01-01

Over the past decades, asthma and allergic diseases, such as allergic rhinitis and eczema, have become increasingly common, but the reason for this increased prevalence is still unclear. It has become apparent that genetic variation alone is not sufficient to account for the observed changes; rather, the changing environment, together with alterations in lifestyle and eating habits, are likely to have driven the increase in prevalence, and in some cases, severity of disease. This is particularly highlighted by recent awareness of, and concern about, the exposure to ubiquitous environmental pollutants, including chemicals with oxidant-generating capacities, and their impact on the human respiratory and immune systems. Indeed, several epidemiological studies have identified a variety of risk factors, including ambient pollutant gases and airborne particles, for the prevalence and the exacerbation of allergic diseases. However, the responsible pollutants remain unclear and the causal relationship has not been established. Recent studies of cellular and animal models have suggested several plausible mechanisms, with the most consistent observation being the direct effects of particle components on the generation of reactive oxygen species (ROS) and the resultant oxidative stress and inflammatory responses. This review attempts to highlight the experimental findings, with particular emphasis on several major mechanistic events initiated by exposure to particulate matters (PMs) in the exposure-disease relationship. PMID:25694815

Neurotrophins in healthy and diseased skin.

PubMed

Raap, U; Kapp, A

2010-04-01

Understanding the complex mechanism of allergic inflammatory skin diseases has been a main challenge of clinical and experimental research for years. It is well known that the inflammatory response is also controlled by tissue resident cells including neurons and structural cells. Thus, allergic inflammation triggers neuronal dysfunction and structural changes in diseased skin. Prime candidates for the interaction between immune, structural, and neuronal cells are presented by neurotrophins. Neurotrophins have initially been described for their neurotrophic capacity. However, recent evidence emerges that neurotrophins display bidirectional interaction pathways in activating structural cells, immune cells in addition to neurons. Neurotrophins including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are upregulated in allergic inflammatory skin diseases. Further, structural cells, neurons and tissue resident cells have not only been shown to be a target but also a source of neurotrophin. In this regard, eosinophil granulocytes which are key target effector cells in chronic inflammatory skin have been identified as a target of neurotrophins but are also capable of neurotrophin production. Thus, neuroimmune interaction mechanisms in allergic inflammatory skin display a novel pathophysiological aspect in which neurotrophins serve as prime candidates for bidirectional interaction mechanisms. In this review, we provide an actual overview of neurotrophins in healthy and diseased skin with special emphasis on atopic dermatitis and therapeutic implications.

The frequency of urinary tract infection and subclinical bacteriuria in dogs with allergic dermatitis treated with oclacitinib: a prospective study.

PubMed

Simpson, Andrew C; Schissler, Jennifer R; Rosychuk, Rod A W; Moore, A Russell

2017-10-01

Oclacitinib is a selective Janus kinase inhibitor for the treatment of canine allergic pruritus and atopic dermatitis in dogs. Glucocorticoids and ciclosporin increase urinary tract infection (UTI) frequency in dogs with inflammatory skin disease. Prospective study to evaluate the frequency of UTI and subclinical bacteriuria in dogs with allergic dermatitis receiving oclacitinib. Client-owned dogs ≥2 years of age with a history of allergic dermatitis without apparent history of urinary tract disease or predisposition to UTI were included. Prior to enrolment, urinalysis and quantitative urine culture were performed after a washout period of at least 14 days from systemic antimicrobial drugs and 28 days for ciclosporin and systemic glucocorticoids. Dogs received oclacitinib at labelled dosing for an intended period of 180-230 days with a follow-up urinalysis and urine culture performed regardless of urinary tract signs. Systemic antimicrobial and immune-modulating drugs were not administered during the study. None of the 55 dogs in this study developed UTI while receiving oclacitinib based on follow-up urinalysis and urine culture performed during a range of 58-280 days (mean 195 days). Two dogs developed self-limiting abnormal urinary tract signs without urine culture or urinalysis findings consistent with UTI. These findings indicate that bacteriuria is not an expected adverse effect in dogs treated with oclacitinib without a prior history of UTI or predisposing condition during this treatment period. Therefore, routine urine culture is not indicated for such dogs in the absence of abnormal urinalysis or clinical signs of urinary tract disease. © 2017 ESVD and ACVD.

Prevention of oral food allergy sensitization via skin application of food allergen in a mouse model.

PubMed

Li, W; Zhang, Z; Saxon, A; Zhang, K

2012-05-01

Treatment options for food allergy remain limited. Development of novel approaches for the prevention and/or treatment of severe peanut allergy and other food allergies is urgently needed. The objective of this study was to test whether skin application of food allergen can be used as a prophylactic and/or therapeutic intervention for food allergy. Balb/C mice were given 5 weekly cutaneous application of complete peanut extract (CPE) or ovalbumin (OVA) ranging from 10 to 1000 μg on the shaved back skin, followed by 5 weekly treatments with oral CPE or OVA plus cholera toxin to induce allergic reactivity to the food. At various time points, the immunologic responses and allergic clinical manifestations to allergens were examined. Skin application of a 10-1000 μg dose of CPE or OVA to structurally intact skin did not lead to allergic sensitization to peanut or OVA. Rather, cutaneous allergen application blocked, in a dose-dependent fashion, the subsequent induction of the oral sensitization including inhibiting oral sensitization-induced CPE-specific IgE, IgG1, and IgG2a production, suppressing the peanut anaphylaxis, and modulating the oral sensitization-promoted cytokine production. The cutaneous OVA application also resulted in similar results as seen with CPE application. Cutaneous application of intact skin with peanut or OVA can block the development of orally induced corresponding food allergies, suggesting that allergic tolerance to peanuts and OVA might be achieved via allergen cutaneous application. © 2012 John Wiley & Sons A/S.

Inhibitory effects of bee venom on mast cell-mediated allergic inflammatory responses.

PubMed

Kang, Yun-Mi; Chung, Kyung-Sook; Kook, In-Hoon; Kook, Yoon-Bum; Bae, Hyunsu; Lee, Minho; An, Hyo-Jin

2018-06-01

Although bee venom (BV) is a toxin that causes bee stings to be painful, it has been widely used clinically for the treatment of certain immune‑associated diseases. BV has been used traditionally for the treatment of chronic inflammatory diseases. In this regard, the present study analyzed the effect of BV on the regulation of inflammatory mediator production by mast cells and their allergic inflammatory responses in an animal model. HMC‑1 cells were treated with BV prior to stimulation with phorbol‑12‑myristate 13‑acetate plus calcium ionophore A23187 (PMACI). The production of allergy‑associated pro‑inflammatory mediators was examined, and the underlying mechanisms were investigated. Furthermore, to investigate whether BV exhibits anti‑inflammatory effects associated with anti‑allergic effects in vivo, a compound 48/80‑induced anaphylaxis model was used. BV inhibited histamine release, mRNA expression and production of cytokines in the PMACI‑stimulated HMC‑1 cells. Furthermore, the inhibitory effects of BV on mitogen‑activated protein kinase (MAPK), MAPK kinase, signal transducer and activator of transcription 3 (STAT3) and Akt were demonstrated. The present study also investigated the ability of BV to inhibit compound 48/80‑induced systemic anaphylaxis in vivo. BV protected the mice against compound 48/80‑induced anaphylactic‑associated mortality. Furthermore, BV suppressed the mRNA expression levels of pro‑inflammatory cytokines, and suppressed the activation of MAPK and STAT3 in this model. These results provide novel insights into the possible role of BV as a modulator for mast cell‑mediated allergic inflammatory disorders.

THE INFLUENCE OF PARTICULATE AIR POLLUTANTS ON ALLERGIC SENSITIZATION IN ANIMAL MODELS

EPA Science Inventory

Air pollution has long been associated with detrimental health risks in susceptible populations including asthmatics. Experimental evidence in rodents indicates that inhaled or instilled air pollutants such as diesel exhaust particles (DEPs), residual oil fly ash or its constitu...

The Role of TNF Family Molecules Light in Cellular Interaction Between Airway Smooth Muscle Cells and T Cells During Chronic Allergic Inflammation.

PubMed

Shi, Fei; Xiong, Yi; Zhang, Yarui; Qiu, Chen; Li, Manhui; Shan, Aijun; Yang, Ying; Li, Binbin

2018-06-01

Interaction between T cells and airway smooth muscle (ASM) cells has been identified as an important factor in the development of asthma. LIGHT (known as TNFSF14) -mediated signaling likely contributes to various inflammatory disorders and airway remodeling. The objective of this study was to investigate the roles of LIGHT-mediated pathways in the interaction between ASM cells and T cells during chronic allergic inflammation. Mice were sensitized and challenged by ovalbumin (OVA) to induce chronic airway allergic inflammation. The control group received PBS only. The histological features and LIGHT expressions in lungs were assessed in vivo. Furthermore, T cells and ASM cells derived from the model mice were co-cultured both in the presence and absence of anti-LIGHT Ab for 72 h. The effects of LIGHT blockade on expressions of downstream signaling molecules, proliferation, and apoptosis of ASM cells, differentiation of T cells, and inflammatory cytokines release were evaluated. We demonstrated that LIGHT blockade strikingly inhibited the mRNA and protein expressions of HVEM, c-JUN, and NFκB. Additionally, LIGHT blockade resulted in decreased proliferation and increased apoptosis of ASM cells. Moreover, depletion of LIGHT dramatically reduced the differentiation of CD4 + T cells into Th1, Th2, and Th17 cells, as well as inhibited inflammatory cytokines release including IL-13, TGF-β, and IFN-γ, which are associated with CD4 + T cell differentiation and ASM cell proliferation. LIGHT plays an important role in the interaction between T cells and ASM cells in chronic allergic asthma. Blockade of LIGHT markedly suppressed ASM hyperplasia and inflammatory responses, which might be modulated through HVEM-NFκB or c-JUN pathways. Therefore, targeting LIGHT is a promising therapeutic strategy for airway inflammation and remodeling in chronic allergic asthma.

The possible mechanisms of the human microbiome in allergic diseases.

PubMed

Ipci, Kagan; Altıntoprak, Niyazi; Muluk, Nuray Bayar; Senturk, Mehmet; Cingi, Cemal

2017-02-01

In the present paper, we discuss the importance of the microbiome in allergic disease. In this review paper, the data from the Medline (PubMed) and search engine of Kirikkale University were systematically searched for all relevant articles in June 15th, 2015 for the past 30 years. The keywords of "microbiome", "dysbiosis", "allergy", "allergic rhinitis", "allergic disease", "mechanisms" and "treatment" were used alone or together. In this paper, microbiomes were presented in terms of "Definition", "Influence of \\the human microbiome on health", "The microbiome and allergic diseases", and "Modulation of the gut microbiota in terms of treatment and prevention". Microbiological dysbiosis is also reviewed. The microbiome is the genetic material of all microbes (bacteria, fungi, protozoa, and viruses) that live on or in the human body. Microbes outnumber human cells in a 10:1 ratio. Most microbes live in the gut, particularly the large intestine. Changes in the immune function of the respiratory tract are (at least in theory) linked to the immunomodulatory activity of the gut microbiota via the concept of a "common mucosal response". The gut microbiota shapes systemic immunity, thus affecting the lung mucosa. Alternatively, changes in the gut microbiota may reflect alterations in the oropharyngeal microbiota, which may in turn directly affect the lung microbiota and host immune responses via microaspiration. Dysbiosis is defined as qualitative and quantitative changes in the intestinal flora; and modern diet and lifestyle, antibiotics, psychological and physical stress result in alterations in bacterial metabolism, as well as the overgrowth of potentially pathogenic microorganisms. All immune system components are directly or indirectly regulated by the microbiota. The nature of microbial exposure early in life appears to be important for the development of robust immune regulation; disruption of either the microbiota or the host response can trigger chronic inflammation. Dysbiosis is also an important clinical entity. Antibiotics, psychological and physical stress, and dietary factors contribute to intestinal dysbiosis.

Increase of Frequency and Modulation of Phenotype of Regulatory T Cells by Atorvastatin Is Associated with Decreased Lung Inflammatory Cell Infiltration in a Murine Model of Acute Allergic Asthma

PubMed Central

Blanquiceth, Yurany; Rodríguez-Perea, Ana Lucia; Tabares Guevara, Jorge H.; Correa, Luis Alfonso; Sánchez, María Dulfary; Ramírez-Pineda, José Robinson; Velilla, Paula Andrea

2016-01-01

Regulatory T cells (Tregs) play an important role by controlling allergic inflammation of airways. Recently, it has been shown that statins have immunomodulatory properties, probably mediated by their effects on Tregs. Therefore, we evaluated the in vivo effect of atorvastatin (ATV) on Tregs and its association with the inflammatory process in a model of allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) and then challenged with intranasal OVA. ATV (40 mg/kg) was delivered by daily intraperitoneal injection for 7 or 15 days before each OVA challenge. ATV treatment for 7 days increased the frequency of Tregs in mediastinal lymph nodes (MLN) and the interleukin (IL)-10 in lungs. After 15 days of treatment, ATV increased the percentage of glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+) and programmed cell death protein 1 (PD-1+) Tregs in the lung, without enhancing their suppressive activity, but also increased the percentage of conventional T cells expressing GITR+, PD1+, and OX-40 (tumor necrosis factor receptor superfamily member 4). Although no significant changes were observed in the number of inflammatory cells in the bronchoalveolar lavage (BAL), OVA-specific immunoglobulin E in the serum, and type 2 helper (Th2) cytokines in the lungs, there was a significant decrease of peribronchial inflammation that negatively correlated with the Tregs in MLN and the concentration of IL-10 in the lung. These results suggest that ATV has an immunomodulatory role possibly mediated by their effects on Tregs, which could contribute to the control of inflammation during allergic asthma. Further studies are necessary to elucidate the contribution of Treg to immunomodulatory action of statins in the context of allergic asthma. PMID:28066430

The gut microbiota and inflammatory noncommunicable diseases: associations and potentials for gut microbiota therapies.

PubMed

West, Christina E; Renz, Harald; Jenmalm, Maria C; Kozyrskyj, Anita L; Allen, Katrina J; Vuillermin, Peter; Prescott, Susan L

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity for multisystem effects. Changes in microbial composition are implicated in the increasing propensity for a broad range of inflammatory diseases, such as allergic disease, asthma, inflammatory bowel disease (IBD), obesity, and associated noncommunicable diseases (NCDs). There are also suggestive implications for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti-inflammatory properties. Specific probiotics also have immunomodulatory and metabolic effects. However, when evaluated in clinical trials, the effects are variable, preliminary, or limited in magnitude. Fecal microbiota transplantation is another emerging therapy that regulates inflammation in experimental models. In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Treatment with galectin-1 eye drops regulates mast cell degranulation and attenuates the severity of conjunctivitis.

PubMed

Mello-Bosnic, Claudia; Gimenes, Alexandre Dantas; Oliani, Sonia Maria; Gil, Cristiane Damas

2018-05-31

Galectin-1 (Gal-1) is a β-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation, however the mechanisms by which Gal-1 modulates cellular responses in allergic inflammatory processes have not been fully determined. In this study, we evaluated the therapeutic potential of Gal-1 eye drops in an experimental model of conjunctivitis. Wistar rats received a topical application of compound (C)48/80 (100 mg/ml) into right eyes and a drop of vehicle into the contralateral eye. Another group of rats received Gal-1 (0.3 or 3 μg/eye) or sodium cromoglycate (SCG; 40 mg/ml) in both eyes and, after 15 min, right eye was challenged with C48/80. Conjunctivitis-induced by C48/80 was characterized by severe eyelid oedema and tearing, but clinical signs were ameliorated by eye drop doses of both Gal-1 (0.3/3 μg) and SCG. As expected, an increased proportion of degranulated mast cells (62%, P < 0.01) and lower histamine levels were observed after 6 h of C48/80 challenge, compared to control (32%). This effect was abrogated by Gal-1 and SCG, which reduced mast cell degranulation (31-36%), eosinophil migration and eosinophil peroxidase levels in the eyes. Gal-1 (3 μg) and SCG treatments also decreased IL-4 levels, as well as activation of mitogen activated protein kinases compared to untreated C48/80 eyes. Our findings suggest that Gal-1 eye drops represent a new therapeutic strategy for ocular allergic inflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Toxocara canis and the allergic process

PubMed Central

Zaia, Mauricio Grecco; de Oliveira, Sandra Regina Pereira; de Castro, Cynthia Aparecida; Soares, Edson Garcia; Afonso, Ana; Monnazzi, Luis Gustavo S; Peitl, Oscar; Faccioli, Lúcia Helena; Anibal, Fernanda de Freitas

2015-01-01

The protective effect of infectious agents against allergic reactions has been thoroughly investigated. Current studies have demonstrated the ability of some helminths to modulate the immune response of infected hosts. The objective of the present study was to investigate the relationship between Toxocara canis infection and the development of an allergic response in mice immunised with ovalbumin (OVA). We determined the total and differential blood and bronchoalveolar lavage fluid cells using BALB/c mice as a model. To this end, the levels of interleukin (IL)-4, IL-5 and IL-10 and anti-OVA-IgE were measured using an ELISA. The inflammatory process in the lungs was observed using histology slides stained with haematoxylin and eosin. The results showed an increase in the total number of leukocytes and eosinophils in the blood of infected and immunised animals at 18 days after infection. We observed a slight lymphocytic inflammatory infiltrate in the portal space in all infected mice. Anti-OVA-IgE levels were detected in smaller proportions in the plasma of immunised and infected mice compared with mice that were only infected. Therefore, we concluded that T. canis potentiates inflammation in the lungs in response to OVA, although anti-OVA-IgE levels suggest a potential reduction of the inflammatory process through this mechanism. PMID:26517650

Allergy and allergic mediators in tears.

PubMed

Leonardi, Andrea

2013-12-01

The identification of inflammatory mediators in the tear fluid have been extensively used in ocular allergy to find either a 'disease marker', to better understand the immune mechanisms involved in the ocular surface inflammation, or to identify potential targets for therapeutic interventions. While the clinical characteristics allow a relatively convincing diagnosis of ocular allergic diseases, in the initial, non active phases, or in the chronic stages, the diagnosis may not be clear. Although not highly specific, total tear IgE can be measured with local tests by inserting a paper strip in the lower meniscus. The measurement of tear specific inflammatory markers, such as histamine, tryptase, ECP, IL-4, IL-5 and eotaxin, may be useful for the diagnosis or monitoring ocular allergy. New technologies such as multiplex bead assays, membrane-bound antibody array and proteomic techniques can characterize the distribution of a wide range of bioactive trace proteins in tears. Dozens of mediators, cytokines, chemokines, growth factors, angiogenic modulators, enzymes and inhibitors were thus identified in small tear samples using these techniques, providing the possible identification of specific biomarker for either specific disease or disease activity. However, to date, there is no a single specific laboratory test suitable for the diagnosis and monitoring of allergic conjunctivitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

How Stress and Anxiety Can Alter Immediate and Late Phase Skin Test Responses in Allergic Rhinitis

PubMed Central

Kiecolt-Glaser, Janice K.; Heffner, Kathi L.; Glaser, Ronald; Malarkey, William B.; Porter, Kyle; Atkinson, Cathie; Laskowski, Bryon; Lemeshow, Stanley; Marshall, Gailen D.

2010-01-01

Summary Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4 hours in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms. PMID:19150180

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

PubMed

Bousquet, J; Anto, J M; Akdis, M; Auffray, C; Keil, T; Momas, I; Postma, D S; Valenta, R; Wickman, M; Cambon-Thomsen, A; Haahtela, T; Lambrecht, B N; Lodrup Carlsen, K C; Koppelman, G H; Sunyer, J; Zuberbier, T; Annesi-Maesano, I; Arno, A; Bindslev-Jensen, C; De Carlo, G; Forastiere, F; Heinrich, J; Kowalski, M L; Maier, D; Melén, E; Palkonen, S; Smit, H A; Standl, M; Wright, J; Asarnoj, A; Benet, M; Ballardini, N; Garcia-Aymerich, J; Gehring, U; Guerra, S; Hohman, C; Kull, I; Lupinek, C; Pinart, M; Skrindo, I; Westman, M; Smagghe, D; Akdis, C; Albang, R; Anastasova, V; Anderson, N; Bachert, C; Ballereau, S; Ballester, F; Basagana, X; Bedbrook, A; Bergstrom, A; von Berg, A; Brunekreef, B; Burte, E; Carlsen, K H; Chatzi, L; Coquet, J M; Curin, M; Demoly, P; Eller, E; Fantini, M P; Gerhard, B; Hammad, H; von Hertzen, L; Hovland, V; Jacquemin, B; Just, J; Keller, T; Kerkhof, M; Kiss, R; Kogevinas, M; Koletzko, S; Lau, S; Lehmann, I; Lemonnier, N; McEachan, R; Mäkelä, M; Mestres, J; Minina, E; Mowinckel, P; Nadif, R; Nawijn, M; Oddie, S; Pellet, J; Pin, I; Porta, D; Rancière, F; Rial-Sebbag, A; Saeys, Y; Schuijs, M J; Siroux, V; Tischer, C G; Torrent, M; Varraso, R; De Vocht, J; Wenger, K; Wieser, S; Xu, C

2016-11-01

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses.

PubMed

Radauer-Preiml, Isabella; Andosch, Ancuela; Hawranek, Thomas; Luetz-Meindl, Ursula; Wiederstein, Markus; Horejs-Hoeck, Jutta; Himly, Martin; Boyles, Matthew; Duschl, Albert

2016-01-16

Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule 'corona'. Hence, the 'corona' defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens. Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity. The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was found. In summary, this study presents that conjugation of allergens to ENMs can modulate the human allergic response, and that protease activity can be increased. Graphical Abstract Cross-linking of IgE receptors and degranulation of human basophils due to epitope alignment of nanoparticle-coated allergens.

LOW-DOSE AIRBORNE ENDOTOXIN EXPOSURE ENHANCES BRONCHIAL RESPONSIVENESS TO INHALED ALLERGEN IN ATOPIC ASTHMATICS

EPA Science Inventory

Endotoxin exposure has been associated with both protection against development of TH2-immune responses during childhood and exacerbation of asthma in persons who already have allergic airway inflammation.1 Occupational and experimental inhalation exposures to endotoxin have been...

Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis.

PubMed

Keszthelyi, E; Karlik, S; Hyduk, S; Rice, G P; Gordon, G; Yednock, T; Horner, H

1996-10-01

The leukocyte integrin receptor, alpha 4 beta 1, and its endothelial cell ligand, vascular cell adhesion molecule 1, appear to be of critical importance in the leukocyte trafficking that accompanies CNS damage in experimental allergic encephalomyelitis (EAE). In this study, the persistence of the role for alpha 4 beta 1/VCAM-1 in EAE was established by observing antibody-mediated disease reversal up to 1 month following disease onset. Limited treatment with a monoclonal antibody against alpha 4 integrin, GG5/3, resulted in a significant decrease in both clinical and histopathologic signs. This was not observed in isotype control experiments. In the latter phase of progressive disease, widespread demyelination occurred in the animals that did not respond to 6 days of anti-alpha 4 treatment. These results demonstrate an essential role for alpha 4 beta 1 interactions throughout active EAE and illustrate the difference between reversible clinical deficits caused by edema and irreversible deficits associated with demyelination.

Sequence of Tissue Responses in the Early Stages of Experimental Allergic Encephalomyelitis (EAE): Immunohistochemical, Light Microscopic, and Ultrastructural Observations in the Spinal Cord

NASA Technical Reports Server (NTRS)

DAmelio, Fernando E.; Smith, Marion E.; Eng, Lawrence F.

1990-01-01

Experimental allergic encephalomyelitis (EAE) was induced in adult Lewis rats with purified guinea pig CNS myelin and Freund's adjuvant. As soon as the very earliest clinical signs appeared the animals were perfused with fixatives and the spinal cord analyzed by electron microscopy, silver methods, and immunocytochemistry. Our findings suggest that in the early stages of EAE a sequence of events can be traced, although these events frequently overlap. The earliest morphological change appears to be astrocytic edema in both the cell body and processes. Increased amounts of glycogen particles and dispersion of glial filaments are prominent. These changes seem to occur just prior to the time when inflammatory cells begin to penetrate the capillary walls. Invasion of the neuropil mainly by macrophages and lymphocytes closely follows. Both macrophages and microglia seem to participate in phagocytosis of oligodendrocytes and myelin. Demyelination, however, is not a prominent feature at this early stage.

Dysregulation of type 2 innate lymphoid cells and TH2 cells impairs pollutant-induced allergic airway responses.

PubMed

De Grove, Katrien C; Provoost, Sharen; Hendriks, Rudi W; McKenzie, Andrew N J; Seys, Leen J M; Kumar, Smitha; Maes, Tania; Brusselle, Guy G; Joos, Guy F

2017-01-01

Although the prominent role of T H 2 cells in type 2 immune responses is well established, the newly identified type 2 innate lymphoid cells (ILC2s) can also contribute to orchestration of allergic responses. Several experimental and epidemiologic studies have provided evidence that allergen-induced airway responses can be further enhanced on exposure to environmental pollutants, such as diesel exhaust particles (DEPs). However, the components and pathways responsible remain incompletely known. We sought to investigate the relative contribution of ILC2 and adaptive T H 2 cell responses in a murine model of DEP-enhanced allergic airway inflammation. Wild-type, Gata-3 +/nlslacZ (Gata-3-haploinsufficient), RAR-related orphan receptor α (RORα) fl/fl IL7R Cre (ILC2-deficient), and recombination-activating gene (Rag) 2 -/- mice were challenged with saline, DEPs, or house dust mite (HDM) or DEP+HDM. Airway hyperresponsiveness, as well as inflammation, and intracellular cytokine expression in ILC2s and T H 2 cells in the bronchoalveolar lavage fluid and lung tissue were assessed. Concomitant DEP+HDM exposure significantly enhanced allergic airway inflammation, as characterized by increased airway eosinophilia, goblet cell metaplasia, accumulation of ILC2s and T H 2 cells, type 2 cytokine production, and airway hyperresponsiveness compared with sole DEPs or HDM. Reduced Gata-3 expression decreased the number of functional ILC2s and T H 2 cells in DEP+HDM-exposed mice, resulting in an impaired DEP-enhanced allergic airway inflammation. Interestingly, although the DEP-enhanced allergic inflammation was marginally reduced in ILC2-deficient mice that received combined DEP+HDM, it was abolished in DEP+HDM-exposed Rag2 -/- mice. These data indicate that dysregulation of ILC2s and T H 2 cells attenuates DEP-enhanced allergic airway inflammation. In addition, a crucial role for the adaptive immune system was shown on concomitant DEP+HDM exposure. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema

Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples weremore » obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.« less

Immune modulation using transdermal photodynamic therapy

NASA Astrophysics Data System (ADS)

Levy, Julia G.; Chowdhary, R. K.; Ratkay, Leslie G.; Waterfield, Douglas; Obochi, Modestus; Leong, Simon; Hunt, David W. C.; Chan, Agnes H.

1995-01-01

The photosensitizer benzoporphyrin derivative monoacid ring A (VerteporfinR or BPD) has maximum absorption characteristics (690 nm) and biodistribution characteristics which permit activation of the drug in capillaries of the skin without causing skin photosensitivity (transdermal PDT). This permits targeting of cells in the circulation for selective ablation. Since BPD has been shown to accumulate preferentially in activated lymphocytes and monocytes, studies have been undertaken to determine the effect of transdermal PDT on murine models for rheumatoid arthritis (the MRL/lpr adjuvant enhanced model) and multiple sclerosis (the experimental allergic encephalomyelitis (EAE) model in PL mice). Localized transdermal PDT with BPD was found to be completely successful in preventing the development of adjuvant enhanced arthritis in the MRL/lpr mouse as well as improving the underlying arthritic condition of these animals. In the EAE model, in which an adoptive transfer system was used, it was found that transdermal PDT of recipients was effective in preventing EAE if treatments were implemented up to 24 hours after cell transfer but was not effective if given later, indicating the requirement for circulating T cells for effective treatment.

Participation of CD11b and F4/80 molecules in the conjunctival eosinophilia of experimental allergic conjunctivitis.

PubMed

Fukushima, Atsuki; Ishida, Waka; Ojima, Ayako; Kajisako, Mina; Sumi, Tamaki; Yamada, Jun; Tsuru, Emi; Miyazaki, Jun-ichi; Tominaga, Akira; Yagita, Hideo

2010-01-01

CD11b and F4/80 are macrophage surface markers. How these molecules participate in allergic eosinophil infiltration remains unclear. We examined the roles CD11b and F4/80 play in the conjunctival eosinophil infiltration associated with experimental allergic conjunctivitis. Ragweed-immunized BALB/c mice were challenged with ragweed in eye drops to induce conjunctival eosinophil infiltration. The effect of challenge on conjunctival CD11b+ and F4/80+ cell numbers was determined by immunohistochemistry. In the same model, blocking anti-CD11b and anti-F4/80 Abs were injected intraperitoneally during the induction or the effector phase, or subconjunctivally 2 h before challenge, to determine their effect on challenge-induced conjunctival eosinophilia. To examine whether eosinophils express CD11b and F4/80 molecules, splenocytes from IL-5 gene-electroporated mice were subjected to flow cytometric analysis. To clarify the involvement of CD11b and F4/80 in conjunctival eosinophil infiltration, mice were intraperitoneally injected with anti-CD11b and anti-F4/80 Abs and then subconjunctivally injected with eotaxin to induce conjunctival eosinophilia. Ragweed challenge elevated conjunctival CD11b+ and F4/80+ cell numbers. Systemic anti-CD11b and anti-F4/80 Ab treatments during the effector phase, but not in either the induction phase or the local injection of Ab, suppressed conjunctival eosinophil infiltration in ragweed-induced conjunctivitis. Most splenic eosinophils from IL-5 gene-introduced mice expressed CD11b and F4/80. Systemic anti-CD11b and anti-F4/80 Ab treatment suppressed conjunctival eosinophilia induced by subconjunctival eotaxin injection. CD11b and F4/80 appear to participate in conjunctival eosinophil infiltration in allergic conjunctivitis. Their involvement in conjunctival eosinophilia appears to be due to their expression on eosinophils rather than on macrophages. 2009 S. Karger AG, Basel.

A randomized controlled study of peanut oral immunotherapy (OIT): clinical desensitization and modulation of the allergic response

PubMed Central

Varshney, Pooja; Jones, Stacie M.; Scurlock, Amy M.; Perry, Tamara T.; Kemper, Alex; Steele, Pamela; Hiegel, Anne; Kamilaris, Janet; Carlisle, Suzanne; Yue, Xiaohong; Kulis, Mike; Pons, Laurent; Vickery, Brian; Burks, A. Wesley

2011-01-01

Background Open-label oral immunotherapy (OIT) protocols have been used to treat small numbers of patients with peanut allergy. Peanut OIT has not been evaluated in double-blind, placebo-controlled trials. Objective To investigate the safety and effectiveness of OIT for peanut allergy in a double blind, placebo-controlled study. Methods In this multicenter study, peanut-allergic children ages 1-16 years received OIT with peanut flour or placebo. Initial escalation, build-up, and maintenance phases were followed by an oral food challenge at approximately one year. Titrated skin prick tests (SPT) and laboratory studies were performed at regular intervals. Results Twenty-eight subjects were enrolled in the study. Three peanut OIT subjects withdrew early in the study due to allergic side effects. During the double-blind, placebo-controlled food challenge, all remaining peanut OIT subjects (N=16) ingested the maximum cumulative dose of 5000 mg (approximately 20 peanuts), while placebo subjects (N=9) ingested a median cumulative dose of 280 mg (range, 0-1900 mg) [p<0.001]. In contrast to the placebo group, the peanut OIT group showed reductions in SPT size (p<0.001), IL-5 (p=0.01), and IL-13 (p=0.02) and increases in peanut-specific IgG4 (p<0.001). Peanut OIT subjects had initial increases in peanut-specific IgE (p<0.01) but did not show significant change from baseline by the time of OFC. The ratio of FoxP3 hi: FoxP3 intermediate CD4+CD25+ T cells increased at the time of OFC (p=0.04) in peanut OIT subjects. Conclusion These results conclusively demonstrate that peanut OIT induces desensitization and concurrent immune modulation. The present study continues and is evaluating the hypothesis that peanut OIT causes long-term immune tolerance. PMID:21377034

Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma.

PubMed

Moore, Brian D; Hyde, Dallas; Miller, Lisa; Wong, Emily; Frelinger, Jessica; Schelegle, Edward S

2012-01-01

Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O(3)) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O(3) and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O(3) or in combination (HDMA+O(3)). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT(2), 5-HT(3) and 5-HT(4) receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT(2), 5-HT(3) and 5-HT(4) receptors. Conversely, a 5-HT(1) receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. HDMA, O(3) and HDMA+O(3) exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT(2), 5-HT(3) and 5-HT(4) receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT(1) receptors located on ASM. Copyright © 2012 S. Karger AG, Basel.

Topical royal jelly alleviates symptoms of pruritus in a murine model of allergic contact dermatitis

PubMed Central

Yamaura, Katsunori; Tomono, Ayana; Suwa, Eriko; Ueno, Koichi

2013-01-01

Background: Royal jelly is widely used as a health tonic, especially in Asia. Royal jelly is commonly used in cosmetics as well as in dietary supplements and beverages. Little is known, however, about the pharmacologic efficacy of topical royal jelly. Therefore, we investigated the antipruritic activity of topical royal jelly on chronic pruritus in experimental allergic contact dermatitis in mice. Materials and Methods: Hairless mice (HOS: HR-1), with chronic allergic contact dermatitis induced by 5 weeks of repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to the entire back skin were treated topically with royal jelly (0.01% or 1%) for 5 weeks after sensitization with TNCB. The effects of royal jelly on pruritus and inflammation were evaluated by measurement of scratching behavior and skin inflammation score, respectively. Results: Repeated application of TNCB to the back skin of mice elicited frequent scratching behavior immediately and 24h after challenge. Topical royal jelly (0.01% or 1%) and betamethasone (0.01%) significantly ameliorated this chronic pruritus throughout the experimental period. The level of nerve growth factor mRNA in back skin was increased in the mice with dermatitis and reduced by betamethasone, but not by royal jelly. Conclusion: The inhibitory effect of royal jelly on chronic pruritus may occur through different mechanisms from those of betamethasone. Topical application of royal jelly, as used in cosmetics, might be beneficial for the alleviation of chronic pruritus. PMID:23661987

Comparison of Timothy grass pollen extract- and single major allergen-induced gene expression and mediator release in airway epithelial cells: a meta-analysis.

PubMed

Röschmann, K I L; van Kuijen, A-M; Luiten, S; Jonker, M J; Breit, T M; Fokkens, W J; Petersen, A; van Drunen, C M

2012-10-01

Seasonal allergic rhinitis (AR) is a global health problem and its prevalence has increased considerably in the last decades. As the allergic response with its clinical manifestations is triggered by only a few proteins within natural extracts, there is an increasing tendency for single-component-resolved diagnosis and immunotherapy. As natural exposure is not to single proteins, but to complex mixtures of molecules, we were interested in comparing the activation of respiratory epithelial cells induced by the purified major allergen Phl p 1 with the induction caused by a complete extract of Timothy grass pollen (GPE). NCI-H292 cells were exposed to GPE or Ph1 p 1 for 24 h, isolated RNA and cell culture supernatants were used for microarray analysis, multiplex enzyme-linked immunosorbant assay (ELISA) and subsequent analysis. We found 262 genes that showed a GPE-induced change of at least 3-fold, whereas Ph1 p 1-stimulation resulted in 71 genes with a fold induction of more than 3-fold. Besides genes that were regulated by both stimuli, we also detected genes displaying an opposite response after stimulation, suggesting that GPE might be more than purified major allergens with regard to induced immune responses. Additional components within GPE and the resulting modulation of general processes affecting gene transcription and signalling pathways might be crucial to maintain/overcome the diseased phenotype and to induce the influx of cells contributing to late-phase allergic responses. When the initial process of sensitization is the matter of interest or late-phase allergic responses, one might miss important immune modulatory molecules and their interaction with allergens by applying single components only. © 2012 Blackwell Publishing Ltd.

Aggression behaviour induced by oral administration of the Janus-kinase inhibitor tofacitinib, but not oclacitinib, under stressful conditions.

PubMed

Fukuyama, Tomoki; Tschernig, Thomas; Qi, Yulin; Volmer, Dietrich A; Bäumer, Wolfgang

2015-10-05

Janus kinase (JAK) inhibitors have recently been developed for allergic diseases. We focused on the 2 different JAK inhibitors, tofacitinib (selective for JAK3) and oclacitinib (selective for JAK1 and 2), to clarify the mechanism of anti-inflammatory and anti-itching potency of these drugs. In the process of detecting anti-itching potency, we observed that tofacitinib treated mice showed aggression behaviour. The objective of the study reported here was to investigate the aggressive behaviour induced by tofacitinib by using a mouse model of allergic dermatitis and the resident-intruder test. For the allergic dermatitis model, female BALB/c mice were sensitised and challenged topically with toluene-2,4-diisocyanate (TDI). Vehicle, tofacitinib or oclacitinib, was administered orally 30 min before TDI challenge. Scratching, aggression and standing behaviours were monitored in the 60 min period immediately following challenge of TDI. Another group of male BALB/c mice treated with vehicle, tofacitinib or oclacitinib was evaluated in the resident-intruder test and brains were obtained to determine blood brain barrier penetration. In the allergic dermatitis model, a significant increase in aggression and standing behaviour was only obvious in the tofacitinib treatment group. There was no effect in non-sensitised mice, but similar aggression was also induced by tofacitinib in male resident-intruder test. Penetration of blood-brain barrier was observed both in tofacitinib and oclacitinib treated mice. These results suggest that aggression was induced by tofacitinib under some kind of stressful environment. This study indicates a possible role of the JAK-STAT pathway in modulation of aggression behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization

PubMed Central

Savage, Jessica H.; Matsui, Elizabeth C.; Wood, Robert A.; Keet, Corinne A.

2013-01-01

Background Endocrine-disrupting compounds (EDCs) have immune-modulating effects. We were interested in determining their association with allergic sensitization. Objective To determine the association between EDCs and allergic sensitization and if this relationship depended on the antimicrobial properties of the EDCs and/or gender. Methods Data were obtained from the 2005–2006 National Health and Nutrition Examination Survey in which urinary bisphenol A, triclosan, benzophenone-3, and propyl, methyl, butyl and ethyl paraben, and specific IgE were available on 860 children. Aeroallergen and food sensitization were defined as having at least one positive (≥0.35 kU/L) specific IgE to an aeroallergen or a food. Logistic regression was used to determine the association of EDCs and sensitization. Analyses were adjusted for urinary creatinine, age, ethnicity, and poverty index ratio. Results The odds of aeroallergen sensitization significantly increased with the level of the antimicrobial EDCs triclosan and propyl and butyl paraben (p≤0.04). The odds of food sensitization significantly increased with the level of urinary triclosan among male subjects (odds ratio for 3rd versus 1st tertile 3.9, p=0.02 for trend). There was a significant interaction between gender and triclosan, with males being more likely to be food sensitized with exposure (p=0.03). Similar associations were not identified for the non-antimicrobial EDCs bisphenol A and benzophenone-3 (p>0.2). Conclusions As a group, EDCs are not associated with allergen sensitization. However, levels of the antimicrobial EDCs triclosan and parabens were significantly associated with allergic sensitization. The potential role of antimicrobial EDCs in allergic disease warrants further study as they are commonly used in Western society. PMID:22704536

A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

PubMed Central

Klier, John; Geis, Sabine; Steuer, Jeanette; Geh, Katharina; Reese, Sven; Fuchs, Sebastian; Mueller, Ralf S.; Winter, Gerhard

2017-01-01

Abstract Introduction New therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T‐regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T‐helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle‐CpG formulation (CpG‐GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a model for human asthma. Methods Twenty equine asthma‐affected horses were treated either with CpG‐GNP alone or CpG‐GNP with allergens. Two specific allergens were selected for each horse based on history and an in‐vitro test. Each horse received seven administrations of the respective nebulized composition and was examined before treatment, immediately after and 6 weeks after the treatment course. Results Clinical parameters such as breathing rate, indirect interpleural measurement, arterial blood gases, amount of tracheal mucus and percentage of neutrophils and cytokines in tracheal washes and serum samples were evaluated. Treatment with CpG‐GNP alone as well as in combinations with relevant allergens resulted in clinical improvement of nasal discharge, breathing rate, amount of secretion and viscosity, neutrophil percentage and partial oxygen pressure directly after and 6 weeks after treatment. There were no significant differences between the two treatments in clinical parameters or local cytokine profiles in the tracheal wash fluid (IL‐10, IFN‐g, and IL‐17). IL‐4 concentrations decreased significantly in both groups. Conclusion Nonspecific CpG‐GNP‐based immunotherapy shows potential as a treatment for equine and possibly also human allergic asthma. PMID:29094511

Maternal immune response to helminth infection during pregnancy determines offspring susceptibility to allergic airway inflammation.

PubMed

Straubinger, Kathrin; Paul, Sabine; Prazeres da Costa, Olivia; Ritter, Manuel; Buch, Thorsten; Busch, Dirk H; Layland, Laura E; Prazeres da Costa, Clarissa U

2014-12-01

Schistosomiasis, a chronic helminth infection, elicits distinct immune responses within the host, ranging from an initial TH1 and subsequent TH2 phase to a regulatory state, and is associated with dampened allergic reactions within the host. We sought to evaluate whether non-transplacental helminth infection during pregnancy alters the offspring's susceptibility to allergy. Ovalbumin-induced allergic airway inflammation was analyzed in offspring from Schistosoma mansoni-infected mothers mated during the TH1, TH2, or regulatory phase of infection. Embryos derived from in vitro fertilized oocytes of acutely infected females were transferred into uninfected foster mice to determine the role of placental environment. The fetomaternal unit was further characterized by helminth-specific immune responses and microarray analyses. Eventually, IFN-γ-deficient mice were infected to evaluate the role of this predominant cytokine on the offspring's allergy phenotype. We demonstrate that offspring from schistosome-infected mothers that were mated in the TH1 and regulatory phases, but not the TH2 immune phase, are protected against the onset of allergic airway inflammation. Interestingly, these effects were associated with distinctly altered schistosome-specific cytokine and gene expression profiles within the fetomaternal interface. Furthermore, we identified that it is not the transfer of helminth antigens but rather maternally derived IFN-γ during the acute phase of infection that is essential for the progeny's protective immune phenotype. Overall, we present a novel immune phase-dependent coherency between the maternal immune responses during schistosomiasis and the progeny's predisposition to allergy. Therefore, we propose to include helminth-mediated transmaternal immune modulation into the expanded hygiene hypothesis. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Abrogation of Airway Hyperresponsiveness but not Inflammation by Rho kinase Insufficiency

PubMed Central

Kasahara, David I.; Ninin, Fernanda M.C.; Wurmbrand, Allison P.; Liao, James K.; Shore, Stephanie A.

2015-01-01

Background Major features of allergic asthma include airway hyperresponsiveness (AHR), eosinophilic inflammation, and goblet cell metaplasia. Rho kinase (ROCK) is a serine/threonine protein kinase that regulates the actin cytoskeleton. By doing so, it can modulate airway smooth muscle cell contraction and leukocyte migration and proliferation. This study was designed to determine the contributions of the two ROCK isoforms, ROCK1 and ROCK2, to AHR, inflammation and goblet cell metaplasia in a mast-cell dependent model of allergic airways disease. Methods and Results Repeated intranasal challenges with OVA caused AHR, eosinophilic inflammation, and goblet cell hyperplasia in wildtype (WT) mice. OVA-induced AHR was partially or completely abrogated in mice haploinsufficient for ROCK2 (ROCK2+/−) or ROCK1 (ROCK1+/−), respectively. In contrast, there was no effect of ROCK insufficiency on allergic airways inflammation, although both ROCK1 and ROCK2 insufficiency attenuated mast cell degranulation. Goblet cell hyperplasia, as indicated by PAS staining, was not different in ROCK1+/− versus WT mice. However, in ROCK2+/− mice, goblet cell hyperplasia was reduced in medium but not large airways. Maximal acetylcholine-induced force generation was reduced in tracheal rings from ROCK1+/− and ROCK2+/− versus WT mice. The ROCK inhibitor, fasudil, also reduced airway responsiveness in OVA-challenged mice, without affecting inflammatory responses. Conclusion In a mast cell model of allergic airways disease, ROCK1 and ROCK2 both contribute to AHR, likely through direct effects on smooth muscle cell and effects on mast-cell degranulation. In addition, ROCK2 but not ROCK1 plays a role in allergen-induced goblet cell hyperplasia. PMID:25323425

Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

PubMed

Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

2012-12-01

Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

The anti-allergic activity of Cymbopogon citratus is mediated via inhibition of nuclear factor kappa B (Nf-Κb) activation.

PubMed

Santos Serafim Machado, Marta; Ferreira Silva, Hugo Bernardino; Rios, Raimon; Pires de Oliveira, Anaque; Vilany Queiroz Carneiro, Noma; Santos Costa, Ryan; Santos Alves, William; Meneses Souza, Fabio-Luis; da Silva Velozo, Eudes; Alves de Souza, Silvana; Sarmento Silva, Tania Maria; Silva, Maria Lenise; Pontes-de-Carvalho, Lain Carlos; Alcântara-Neves, Neuza Maria; Figueiredo, Camila Alexandrina

2015-06-06

The prevalence of allergic diseases such as asthma has significantly increased worldwide, making it a public health concern. There is an urgent need for new anti-inflammatory agents with selective pharmacology and lower toxicity. Plant extracts have been used for centuries in traditional medicine to alleviate inflammatory diseases. In this work, we evaluated the anti-allergic activity of Cymbopogon citratus (Cy), a medicinal herb used by folk medicine to treat asthma. We used a murine model of respiratory allergy to the mite Blomia tropicalis (Bt) and evaluated certain parameters known to be altered in this model. A/J mice were sensitized (100 μg/animal s.c.) and challenged (10 μg/animal i.n.) with Bt mite extract and treated with 60, 120 or 180 mg/kg of Cy standardized hexane extract. The parameters evaluated included: cellular infiltrate in bronchoalveolar lavage (BAL); eosinophil peroxidase activity (EPO); histopathological examination of the lung; serum levels of specific IgE, IgG1 and IgG2a; Th2 cytokine concentrations in BAL and expression of NF-κB. Our results showed that oral administration of a Cy hexane extract (especially 180 mg/Kg) reduced the numbers of leukocytes/eosinophils in BAL; the eosinophil peroxidase activity in BAL; the infiltration of leukocytes in lung tissue; the production of mucus in the respiratory tract; the level of IL-4 in BAL and the nuclear expression of NF-κB. The results presented demonstrate the potential of the Cy hexane extract to modulate allergic asthma; this extract may be an alternative future approach to treat this pathology.

Treatment of poison ivy/oak allergic contact dermatitis with an extract of jewelweed.

PubMed

Long, D; Ballentine, N H; Marks, J G

1997-09-01

Jewelweed (Impatiens biflora) is a plant which has been used for centuries for the treatment of poison ivy/oak allergic contact dermatitis. Numerous claims for its effectiveness exist in the lay press, and over-the-counter medicaments containing jewelweed are reputed to be an effective remedy for poison ivy/oak dermatitis. Despite these claims, few scientific studies testing the effectiveness of jewelweed have been performed. Our objective in this pilot study was to test the efficacy of an extract of jewelweed in the treatment of experimentally induced allergic contact dermatitis to poison ivy/oak. A randomized, double-blinded, paired comparison investigation was performed. Ten adult volunteers were patch tested to urushiol, the allergenic resin in poison ivy/oak. For each volunteer, one patch test site was treated with an extract prepared from the fresh stems of jewelweed; the remaining site was treated with distilled water to serve as a control. Sites were examined on days 2, 3, 7, and 9 with reactions graded on a numerical scale. All subjects developed dermatitis at each patch test site. There was no statistically significant difference in the objective scores at the sites treated with jewelweed extract versus the distilled water control sites. This study demonstrated that an extract of jewelweed was not effective in the treatment of poison ivy/oak allergic contact dermatitis.

B-Glucan exacerbates allergic asthma independent of fungal ...

EPA Pesticide Factsheets

BackgroundAllergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity.ObjectiveWe sought to determine the mechanism by which fungi affect asthma development and severity.MethodsWe integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity.ResultsWe report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with β-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc−/− mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity.ConclusionOur data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma. To describe th

Hypnosis and the allergic response.

PubMed

Wyler-Harper, J; Bircher, A J; Langewitz, W; Kiss, A

1994-01-01

In recent years our knowledge of the immune system and the pathogenesis of immune disorders has increased. There has been much research on the complex connections between the psyche, the central nervous system and the immune system and the effect of mood on disease processes. This paper reviews the evidence on the effects of hypnosis on the allergic skin test reaction, on allergies, particularly respiratory allergies and hayfever, and on bronchial hyperreactivity and asthma. Hypnosis, which is generally regarded as an altered state of consciousness associated with concentration, relaxation and imagination, and amongst other characteristics an enhanced responsiveness to suggestion, has long been thought to be effective in the amelioration of various bodily disorders. It has seemed that the state of hypnosis is capable of a bridging or mediating function in the supposed dualism between mind and body. There has been great variation in the experimental and clinical procedures such as type of hypnotic intervention employed, the training of subjects and the timing of the intervention. Also, variability in the type of allergen used and its mode of application is evident. But despite these limitations, many of the studies have shown a link between the use of hypnosis and a changed response to an allergic stimulus or to a lessened bronchial hyperreactivity. There is as yet no clear explanation for the effectiveness of hypnosis, but there is some evidence for an influence on the neurovascular component of the allergic response.

Experimental patch testing with chromium-coated materials.

PubMed

Bregnbak, David; Thyssen, Jacob P; Jellesen, Morten S; Zachariae, Claus; Johansen, Jeanne D

2017-06-01

Chromium coatings on metal alloys can be decorative, and prevent corrosion and metal ion release. We recently showed that handling of a chromium-containing disc resulted in chromium deposition on the skin. To examine patch test reactivity to chromium-coated discs. We included 15 patients: 10 chromium-allergic patients, and 5 patients without chromium allergy. All were patch tested with potassium dichromate, cobalt chloride, nickel sulfate, and nine different metallic discs. The chromium-allergic patients were also patch tested with serial dilutions of potassium dichromate. Positive/weaker reactions were observed to disc B (1 of 10), disc C (1 of 10), and disc D, disc E, and disc I (4 of 10 each). As no controls reacted to any of the discs, the weak reactions indicate allergic reactions. Positive patch test reactions to 1770 ppm chromium(VI) in the serial dilutions of potassium dichromate were observed in 7 of 10 patients. When the case group was narrowed down to include only the patients with a current positive patch test reaction to potassium dichromate, elicitation of dermatitis by both chromium(III) and chromium(VI) discs was observed in 4 of 7 of patients. Many of the patients reacted to both chromium(III) and chromium(VI) surfaces. Our results indicate that both chromium(VI) and chromium(III) pose a risk to chromium-allergic patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Real-time assessment of inflammation and treatment response in a mouse model of allergic airway inflammation

PubMed Central

Cortez-Retamozo, Virna; Swirski, Filip K.; Waterman, Peter; Yuan, Hushan; Figueiredo, Jose Luiz; Newton, Andita P.; Upadhyay, Rabi; Vinegoni, Claudio; Kohler, Rainer; Blois, Joseph; Smith, Adam; Nahrendorf, Matthias; Josephson, Lee; Weissleder, Ralph; Pittet, Mikael J.

2008-01-01

Eosinophils are multifunctional leukocytes that degrade and remodel tissue extracellular matrix through production of proteolytic enzymes, release of proinflammatory factors to initiate and propagate inflammatory responses, and direct activation of mucus secretion and smooth muscle cell constriction. Thus, eosinophils are central effector cells during allergic airway inflammation and an important clinical therapeutic target. Here we describe the use of an injectable MMP-targeted optical sensor that specifically and quantitatively resolves eosinophil activity in the lungs of mice with experimental allergic airway inflammation. Through the use of real-time molecular imaging methods, we report the visualization of eosinophil responses in vivo and at different scales. Eosinophil responses were seen at single-cell resolution in conducting airways using near-infrared fluorescence fiberoptic bronchoscopy, in lung parenchyma using intravital microscopy, and in the whole body using fluorescence-mediated molecular tomography. Using these real-time imaging methods, we confirmed the immunosuppressive effects of the glucocorticoid drug dexamethasone in the mouse model of allergic airway inflammation and identified a viridin-derived prodrug that potently inhibited the accumulation and enzyme activity of eosinophils in the lungs. The combination of sensitive enzyme-targeted sensors with noninvasive molecular imaging approaches permitted evaluation of airway inflammation severity and was used as a model to rapidly screen for new drug effects. Both fluorescence-mediated tomography and fiberoptic bronchoscopy techniques have the potential to be translated into the clinic. PMID:19033674

[Experimental study of metabonomics in the diagnosis of allergic rhinitis in mice].

PubMed

Wang, A; Li, Q F; Zhang, G Q; Zhao, C Q

2016-02-01

To investigate the application of metabonomics in the diagnosis of allergic rhinitis. Eighty male Kunming mice were randomly divided into two groups, control group (30 mice) and allergic rhinitis (AR) group (50 mice). After modeling, removal behavior score more than 6 and retain 30 mice behavior score equal to 6.Collect the mice peripheral blood and preparate blood serum, using UPLC-MS chromatographic separation and detection. The data were pretreated by SPSS and Excel, after chromatographic peak matching by MZmine. Firstly , delete interference data in accordance with the 80% rule .Then, the investigate data were analyzed by PLS-DA and PCA-X. Three-dimensional view of the control group (30 mice) and AR group (30 mice) blood serum data was drawn using PCA-X and PLS-DA method. The two groups of samples could be completely separated through views, which showed that there was a significant difference between the two groups of data. There were some differences in the blood metabolites between the control group and AR group . The study showed that it was scientific and feasible to diagnose AR using the metabonomics.

The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways.

PubMed

Navarro, S; Cossalter, G; Chiavaroli, C; Kanda, A; Fleury, S; Lazzari, A; Cazareth, J; Sparwasser, T; Dombrowicz, D; Glaichenhaus, N; Julia, V

2011-01-01

The prevalence of asthma has steadily increased during the last decade, probably as the result of changes in the environment, including reduced microbial exposure during infancy. Accordingly, experimental studies have shown that deliberate infections with live pathogens prevent the development of allergic airway diseases in mice. Bacterial extracts are currently used in children suffering from repeated upper respiratory tract infections. In the present study, we have investigated whether bacterial extracts, commercially available as Broncho-Vaxom (BV), could prevent allergic airway disease in mice. Oral treatment with BV suppressed airway inflammation through interleukin-10 (IL-10)-dependent and MyD88 (myeloid differentiation primary response gene (88))-dependent mechanisms and induced the conversion of FoxP3 (forkhead box P3)(-) T cells into FoxP3(+) regulatory T cells. Furthermore, CD4(+) T cells purified from the trachea of BV-treated mice conferred protection against airway inflammation when adoptively transferred into sensitized mice. Therefore, treatment with BV could possibly be a safe and efficient strategy to prevent the development of allergic diseases in children.

D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease.

PubMed

Kepert, Inge; Fonseca, Juliano; Müller, Constanze; Milger, Katrin; Hochwind, Kerstin; Kostric, Matea; Fedoseeva, Maria; Ohnmacht, Caspar; Dehmel, Stefan; Nathan, Petra; Bartel, Sabine; Eickelberg, Oliver; Schloter, Michael; Hartmann, Anton; Schmitt-Kopplin, Philippe; Krauss-Etschmann, Susanne

2017-05-01

Chronic immune diseases, such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals, such as probiotics, for the prevention of allergic disease. However, clinical trials have produced inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host's microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty. We sought to identify and characterize a bioactive probiotic metabolite for potential prevention of allergic airway disease. Probiotic supernatants were screened for their ability to concordantly decrease the constitutive CCL17 secretion of a human Hodgkin lymphoma cell line and prevent upregulation of costimulatory molecules of LPS-stimulated human dendritic cells. Supernatants from 13 of 37 tested probiotic strains showed immunoactivity. Bioassay-guided chromatographic fractionation of 2 supernatants according to polarity, followed by total ion chromatography and mass spectrometry, yielded C 11 H 12 N 2 O 2 as the molecular formula of a bioactive substance. Proton nuclear magnetic resonance and enantiomeric separation identified D-tryptophan. In contrast, L-tryptophan and 11 other D-amino acids were inactive. Feeding D-tryptophan to mice before experimental asthma induction increased numbers of lung and gut regulatory T cells, decreased lung T H 2 responses, and ameliorated allergic airway inflammation and hyperresponsiveness. Allergic airway inflammation reduced gut microbial diversity, which was increased by D-tryptophan. D-tryptophan is a newly identified product from probiotic bacteria. Our findings support the concept that defined bacterial products can be exploited in novel preventative strategies for chronic immune diseases. Copyright © 2016. Published by Elsevier Inc.

Multiple independent IgE epitopes on the highly allergenic grass pollen allergen Phl p 5.

PubMed

Levin, M; Rotthus, S; Wendel, S; Najafi, N; Källström, E; Focke-Tejkl, M; Valenta, R; Flicker, S; Ohlin, M

2014-11-01

Group 5 allergens are small proteins that consist of two domains. They belong to the most potent respiratory allergens. To determine the binding sites and to study allergic patients' IgE recognition of the group 5 allergen (Phl p 5) from timothy grass pollen using human monoclonal IgE antibodies that have been isolated from grass pollen allergic patients. Using recombinant isoallergens, fragments, mutants and synthetic peptides of Phl p 5, as well as peptide-specific antibodies, the interaction of recombinant human monoclonal IgE and Phl p 5 was studied using direct binding and blocking assays. Cross-reactivity of monoclonal IgE with group 5 allergens in several grasses was studied and inhibition experiments with patients' polyclonal IgE were performed. Monoclonal human IgE showed extensive cross-reactivity with group 5 allergens in several grasses. Despite its small size of 29 kDa, four independent epitope clusters on isoallergen Phl p 5.0101, two in each domain, were recognized by human IgE. Isoallergen Phl p 5.0201 carried two of these epitopes. Inhibition studies with allergic patients' polyclonal IgE suggest the presence of additional IgE epitopes on Phl p 5. Our results reveal the presence of a large number of independent IgE epitopes on the Phl p 5 allergen explaining the high allergenic activity of this protein and its ability to induce severe allergic symptoms. High-density IgE recognition may be a general feature of many potent allergens and form a basis for the development of improved diagnostic and therapeutic procedures in allergic disease. © 2014 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.

PubMed

Azouz, Nurit P; Ynga-Durand, Mario A; Caldwell, Julie M; Jain, Ayushi; Rochman, Mark; Fischesser, Demetria M; Ray, Leanne M; Bedard, Mary C; Mingler, Melissa K; Forney, Carmy; Eilerman, Matthew; Kuhl, Jonathan T; He, Hua; Biagini Myers, Jocelyn M; Mukkada, Vincent A; Putnam, Philip E; Khurana Hershey, Gurjit K; Kottyan, Leah C; Wen, Ting; Martin, Lisa J; Rothenberg, Marc E

2018-06-06

Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Experimental manipulation strategies reducing SPINK7 in an esophageal epithelial progenitor cell line and primary esophageal epithelial cells were sufficient to induce barrier dysfunction and transcriptional changes characterized by loss of cellular differentiation and altered gene expression known to stimulate allergic responses (for example, FLG and SPINK5 ). Epithelial silencing of SPINK7 promoted production of proinflammatory cytokines including thymic stromal lymphopoietin (TSLP). Loss of SPINK7 increased the activity of urokinase plasminogen-type activator (uPA), which in turn had the capacity to promote uPA receptor-dependent eosinophil activation. Treatment of epithelial cells with the broad-spectrum antiserine protease, α1 antitrypsin, reversed the pathologic features associated with SPINK7 silencing. The relevance of this pathway in vivo was supported by finding genetic epistasis between variants in TSLP and the uPA-encoding gene, PLAU We propose that the endogenous balance between SPINK7 and its target proteases is a key checkpoint in regulating mucosal differentiation, barrier function, and inflammatory responses and that protein replacement with antiproteases may be therapeutic for select allergic diseases. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

PubMed Central

Yi, E. S.; Lee, H.; Suh, Y. K.; Tang, W.; Qi, M.; Yin, S.; Remick, D. G.; Ulich, T. R.

1996-01-01

Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 11 Figure 13 Figure 12 Figure 14 PMID:8863677

Dietary management of peanut and tree nut allergy: what exactly should patients avoid?

PubMed

Brough, H A; Turner, P J; Wright, T; Fox, A T; Taylor, S L; Warner, J O; Lack, G

2015-05-01

Peanut and tree nut allergies are the commonest cause of life-threatening food-allergic reactions and significantly affect quality of life in children and their families. Dietary nut avoidance and provision of emergency medication is currently the mainstay of treatment. Nut avoidance has consequences on both quality of life and nutrition. We review the terminology that may cause confusion and lead to unnecessary dietary restrictions. In peanut or tree nut-allergic children, introduction of specific nuts to which the child is not allergic may improve quality of life and should be considered in patients with multiple foods allergies, vegan or ethnic-specific diets, in whom nuts are an important source of protein. Nut-allergic consumers do not just need to avoid foods containing nuts as an ingredient, but also contend with pre-packed foods which frequently have precautionary allergen labelling (PAL) referring to possible nut contamination. Although the published rate of peanut contamination in 'snack' foods with PAL (see Box ) ranges from 0.9-32.4%, peanut contamination in non-snack items with PAL is far less common. We propose that in some peanut-allergic patients (depending on history of reactivity to trace levels of peanut, reaction severity, other medical conditions, willingness to always carry adrenaline, etc.), consideration may be given to allow the consumption of non-snack foods containing PAL following discussion with the patient's (and their family's) specialist. More work is needed to provide consumers with clearer information on the risk of potential nut contamination in pre-packed food. We also draw attention to the change in legislation in December 2014 that require mandatory disclosure of allergens in non-pre-packed foods. © 2014 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Importance of basophils in eosinophilic asthma: the murine counterpart.

PubMed

Poddighe, D; Mathias, C B; Brambilla, I; Marseglia, G L; Oettgen, H C

2018-01-01

Several experimental studies in mice showed that basophils participate in the initiation of Th2 adaptive immune response, in addition to the effector phase. However, the role of basophils in allergic airway inflammation is less clear. The aim of this experiment was to assess the importance of basophils in recruiting inflammatory cells and, in particular, eosinophils in a murine model of asthma induced by Aspergillus fumigatus allergens. Additionally, bronchial reactivity was evaluated. Basophil depletion resulted in a reduction of inflammatory cells in the airways and eosinophil recruitment was significantly impaired. Also bronchial reactivity seemed to be impaired in basophil-depleted mice, but the result was not statistically significant. According to these preliminary data, basophils seem to influence the local eosinophilic response of allergic asthma.

Measles virus infection of human keratinocytes: Possible link between measles and atopic dermatitis.

PubMed

Gourru-Lesimple, Geraldine; Mathieu, Cyrille; Thevenet, Thomas; Guillaume-Vasselin, Vanessa; Jégou, Jean-François; Boer, Cindy G; Tomczak, Katarzyna; Bloyet, Louis-Marie; Giraud, Celine; Grande, Sophie; Goujon, Catherine; Cornu, Catherine; Horvat, Branka

2017-05-01

Measles virus (MV) infection is marked with a skin rash in the acute phase of the disease, which pathogenesis remains poorly understood. Moreover, the association between measles and progression of skin diseases, such as atopic dermatitis (AD), is still elusive. We have thus analysed the susceptibility of human keratinocytes to MV infection and explore the potential relationship between MV vaccination and the pathogenesis the AD. We performed immunovirological characterisation of MV infection in human keratinocytes and then tested the effect of live attenuated measles vaccine on the progression of AD in adult patients, in a prospective, double-blind study. We showed that both human primary keratinocytes and the keratinocyte cell line HaCaT express MV receptors and could be infected by MV. The infection significantly modulated the expression of several keratinocyte-produced cytokines, known to be implicated in the pathogenesis of inflammatory allergic diseases, including AD. We then analysed the relationship between exposure to MV by vaccination and the progression of AD in 20 adults during six weeks. We found a significant decrease in CCL26 and thymic stromal lymphopoietin (TSLP) mRNA in biopsies from acute lesions of vaccinated patients, suggesting MV-induced modulation of skin cytokine expression. Clinical analysis revealed a transient improvement of SCORAD index in vaccinated compared to placebo-treated patients, two weeks after vaccination. Altogether, these results clearly demonstrate that keratinocytes are susceptible to MV infection, which could consequently modulate their cytokine production, resulting with a beneficial effect in the progression of AD. This study provides thus a proof of concept for the vaccination therapy in AD and may open new avenues for the development of novel strategies in the treatment of this allergic disease. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Attenuated Allergenic Activity of Ovomucoid After Electrolysis

PubMed Central

Kido, Jun

2015-01-01

Ovomucoid (OMC) is the most prominent allergen causing hen's egg allergy, containing disulfide (S-S) bonds that may be responsible for its allergic action. As S-S bonds may be reduced during electrolysis, this study was undertaken to evaluate modulation of the allergic action of OMC after electrolysis. Electrolysis was carried out for 1% OMC containing 1% sodium chloride for 30 minutes with a voltage difference of 90 V, 0.23 A (30 mA/cm2). Protein assays, amino acid measurement, and mass spectrometry in untreated OMC and OMC on both the anode and cathode sides after electrolysis were performed. Moreover, 21 patients with IgE-mediated hen's egg allergy were evaluated by using the skin prick test (SPT) for untreated OMC and OMC after electrolysis. The allergic action of OMC was reduced after electrolysis on both the anode and cathode sides when evaluated by the SPT. The modifications of OMC on electrolysis caused the loss of 2 distinct peptide fragments (57E-63K and 123H-128R) as seen on matrix-associated laser desorption/ionization time-of-flight mass spectrometry. The total free SH groups in OMC were increased on the cathode side. Although the regions of S-S broken bonds were not determined in this study, the change in S-S bonds in OMC on both the anode and cathode sides may reduce the allergenic activity. PMID:26333707

Bromelain Inhibits Allergic Sensitization and Murine Asthma via Modulation of Dendritic Cells

PubMed Central

Secor, Eric R.; Szczepanek, Steven M.; Castater, Christine A.; Adami, Alexander J.; Matson, Adam P.; Rafti, Ektor T.; McNamara, Jeffrey T.; Schramm, Craig M.; Thrall, Roger S.; Silbart, Lawrence K.

2013-01-01

The incidence of atopic conditions has increased in industrialized countries. Persisting symptoms and concern for drug side-effects lead patients toward adjunctive treatments such as phytotherapy. Previously, we have shown that Bromelain (sBr), a mixture of cysteine proteases from pineapple, Ananas comosus, inhibits ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). However, sBr's effect on development of AAD when treatment is administered throughout OVA-alum sensitization was unknown and is the aim of the present study. C57BL/6J mice were sensitized with OVA/alum and challenged with 7 days OVA aerosol. sBr 6 mg/kg/0.5 ml or PBS vehicle were administered throughout sensitization. Lung, bronchoalveolar lavage (BAL), spleen, and lymph nodes were processed for flow cytometry and OVA-specific IgE was determined via ELISA. sBr treatment throughout OVA-alum sensitization significantly reduced the development of AAD (BAL eosinophils and lymphocytes). OVA-specific IgE and OVA TET+ cells were decreased. sBr reduced CD11c+ dendritic cell subsets, and in vitro treatment of DCs significantly reduced CD44, a key receptor in both cell trafficking and activation. sBr was shown to reduce allergic sensitization and the generation of AAD upon antigen challenge. These results provide additional insight into sBr's anti-inflammatory and antiallergic properties and rationale for translation into the clinical arena. PMID:24381635

T regulatory cells: an overview and intervention techniques to modulate allergy outcome

PubMed Central

Nandakumar, Subhadra; Miller, Christopher WT; Kumaraguru, Uday

2009-01-01

Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals. PMID:19284628

[Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases].

PubMed

Liu, Y; Liu, Z

2017-02-07

Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.

Expression and function of Allergin-1 on human primary mast cells.

PubMed

Nagai, Kei; Tahara-Hanaoka, Satoko; Morishima, Yuko; Tokunaga, Takahiro; Imoto, Yoshimasa; Noguchi, Emiko; Kanemaru, Kazumasa; Imai, Masamichi; Shibayama, Shiro; Hizawa, Nobuyuki; Fujieda, Shigeharu; Yamagata, Kunihiro; Shibuya, Akira

2013-01-01

Mast cells (MC) play an important role in allergic and non-allergic immune responses. Activation of human MC is modulated by several cell surface inhibitory receptors, including recently identified Allergin-1 expressed on both human and mouse MC. Although Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice, the expression profile and function of Allergin-1 on human primary MC remains undetermined. Here, we established a seven-color flow cytometry method for assessing expression and function of a very small number of human primary MC. We show that Allergin-1S1, a splicing isoform of Allergin-1, is predominantly expressed on human primary MC in both bronchoalveolar lavage (BAL) fluid and nasal scratching specimens. Moreover, Allergin-1S1 inhibits IgE-mediated activation from human primary MC in BAL fluid. These results indicate that Allergin-1 on human primary MC exhibits similar characteristics as mouse Allergin-1 in the expression profile and function.

Biologic Modulators in Allergic and Autoinflammatory Diseases

PubMed Central

Broderick, Lori; Tourangeau, Louanne M.; Kavanaugh, Arthur; Wasserman, Stephen I.

2011-01-01

Purpose of review The advent of molecular techniques has resulted in the ability to tailor medications to specific protein targets. This review will emphasize several biological therapies, specifically directed toward cytokine receptors and inhibitors, and their role in the treatment of atopic and autoinflammatory diseases. Recent findings Translational research and the identification of the molecular pathophysiology of diseases have led to more targeted treatment approaches. The biologic modulators, encompassing monoclonal antibodies as cytokine inhibitors, receptor blocking antibodies and new fusion receptors are now being applied to diseases beyond their original application. Summary The expanded use of biological therapies has experienced success in the treatment of numerous disorders, especially in subsets of patients with disease that has been refractory to conventional therapies. PMID:21659854

The influence of antigen targeting to sub-cellular compartments on the anti-allergic potential of a DNA vaccine.

PubMed

Weinberger, Esther E; Isakovic, Almedina; Scheiblhofer, Sandra; Ramsauer, Christina; Reiter, Katrin; Hauser-Kronberger, Cornelia; Thalhamer, Josef; Weiss, Richard

2013-12-09

Gene vaccines offer attractive rationales for prophylactic as well as therapeutic treatments of type I allergies. DNA and mRNA vaccines have been shown to prevent from allergic sensitization and to counterbalance established allergic immune reactions. Recent advances in gene vaccine manipulation offer additional opportunities for modulation of T helper cell profiles by specific targeting of cellular compartments. DNA vaccines encoding the major birch pollen allergen Bet v 1.0101 were equipped with different leader sequences to shuttle the antigen to lysosomes (LIMP-II), to trigger cellular secretion (hTPA), or to induce proteasomal degradation via forced ubiquitination (ubi). Mice were pre-vaccinated with these constructs and the protective efficacy was tested by subcutaneous Th2-promoting challenges, followed by allergen inhalation. IgG antibody subclass distribution and allergen-specific IgE as well as cytokine profiles from re-stimulated splenocytes and from BALFs were assessed. The cellular composition of BALFs, and lung resistance and compliance were determined. Immunization with all targeting variants protected from allergic sensitization, i.e. IgE induction, airway hyperresponsiveness, lung inflammation, and systemic and local Th2 cytokine expression. Surprisingly, protection did not clearly correlate with the induction of a systemic Th1 cytokine profile, but rather with proliferating CD4+ CD25+ FoxP3+ T regulatory cells in splenocyte cultures. Targeting the allergen to proteasomal or lysosomal degradation severely down-regulated antibody induction after vaccination, while T cell responses remained unaffected. Although secretion of antigen promoted the highest numbers of Th1 cells, this vaccine type was the least efficient in suppressing the establishment of an allergic immune response. This comparative analysis highlights the modulatory effect of antigen targeting on the resulting immune response, with a special emphasis on prophylactic anti-allergy DNA vaccination. Targeting the antigen to proteasomal or lysosomal degradation reduces the availability of native allergen, thereby rendering the vaccine hypoallergenic without compromising efficacy, an important feature for a therapeutic setting. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Blood-Brain Barrier Permeability and Monocyte Infiltration in Experimental Allergic Encephalomyelitis

ERIC Educational Resources Information Center

Floris, S.; Blezer, E. L. A.; Schreibelt, G.; Dopp, E.; van der Pol, S. M. A.; Schadee-Eestermans, I. L.; Nicolay, K.; Dijkstra, C. D.; de Vries, H. E.

2004-01-01

Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive…

Practical immunoregulation: neonatal immune response variation and prophylaxis of experimental food allergy in pigs.

PubMed

Wilkie, Bruce N; Rupa, Prithy; Schmied, Julie

2012-07-15

The importance of environment in immune response is identified and the increase in prevalence of allergic, autoimmune and chronic inflammatory diseases reviewed. In particular, altered opportunity to acquire evolutionarily anticipated commensal microbiota is associated through the "hygiene hypothesis" with defective developmental and response signals to the innate and adaptive immune systems. Evidence of the detrimental effects of such environments is reviewed as is evidence for remediation using controlled exposure to bacteria or their active components such as LPS or peptidoglycan ligands for TLR and NOD-like receptors. Occurrence of major environmentally associated changes in porcine immune response phenotype are described. The prophylactic effects of heat-killed Escherichia coli given intramuscularly or of oral Lactococcus lactis on experimental ovomucoid-induced allergy in piglets are described in the context of altered immune response bias favouring reduced type-2 phenotypes. The high frequency of clinical tolerance to developing allergic signs even in the face of classical sensitization indicates possible function in this pig model of regulatory effectors such as Treg cells. Copyright © 2011 Elsevier B.V. All rights reserved.

Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares

PubMed Central

Li, Ning; Harkema, Jack R.; Lewandowski, Ryan P.; Wang, Meiying; Bramble, Lori A.; Gookin, Glenn R.; Ning, Zhi; Kleinman, Michael T.; Sioutas, Constantinos

2010-01-01

We have previously demonstrated that intranasal administration of ambient ultrafine particles (UFP) acts as an adjuvant for primary allergic sensitization to ovalbumin (OVA) in Balb/c mice. It is important to find out whether inhaled UFP exert the same effect on the secondary immune response as a way of explaining asthma flares in already-sensitized individuals due to traffic exposure near a freeway. The objective of this study is to determine whether inhalation exposure to ambient UFP near an urban freeway could enhance the secondary immune response to OVA in already-sensitized mice. Prior OVA-sensitized animals were exposed to concentrated ambient UFP at the time of secondary OVA challenge in our mobile animal laboratory in Los Angeles. OVA-specific antibody production, airway morphometry, allergic airway inflammation, cytokine gene expression, and oxidative stress marker were assessed. As few as five ambient UFP exposures were sufficient to promote the OVA recall immune response, including generating allergic airway inflammation in smaller and more distal airways compared with the adjuvant effect of intranasally instilled UFP on the primary immune response. The secondary immune response was characterized by the T helper 2 and IL-17 cytokine gene expression in the lung. In summary, our results demonstrated that inhalation of prooxidative ambient UFP could effectively boost the secondary immune response to an experimental allergen, indicating that vehicular traffic exposure could exacerbate allergic inflammation in already-sensitized subjects. PMID:20562226

Genetics of eosinophilic esophagitis

PubMed Central

Kottyan, LC; Rothenberg, ME

2017-01-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches. PMID:28224995

Genetics of eosinophilic esophagitis.

PubMed

Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

Trichuris suis ova therapy for allergic rhinitis does not affect allergen-specific cytokine responses despite a parasite-specific cytokine response.

PubMed

Bourke, C D; Mutapi, F; Nausch, N; Photiou, D M F; Poulsen, L K; Kristensen, B; Arnved, J; Rønborg, S; Roepstorff, A; Thamsborg, S; Kapel, C; Melbye, M; Bager, P

2012-11-01

Parasitic helminths have been shown to reduce inflammation in most experimental models of allergic disease, and this effect is mediated via cytokine responses. However, in humans, the effects of controlled helminth infection on cytokine responses during allergy have not been studied. The aim was to investigate whether infection with the nematode parasite Trichuris suis alters systemic cytokine levels, cellular cytokine responses to parasite antigens and pollen allergens and/or the cytokine profile of allergic individuals. In a randomized double-blinded placebo-controlled clinical trial (UMIN trial registry, Registration no. R000001298, Trial ID UMIN000001070, URL: http://www.umin.ac.jp/map/english), adults with grass pollen-induced allergic rhinitis received three weekly doses of 2500 Trichuris suis ova (n = 45) or placebo (n = 44) over 6 months. IFN-γ, TNF-α, IL-4, IL-5, IL-10 and IL-13 were quantified via cytometric bead array in plasma. Cytokines, including active TGF-β, were also quantified in supernatants from peripheral blood mononuclear cells cultured with parasite antigens or pollen allergens before, during and after the grass pollen season for a sub-cohort of randomized participants (T. suis ova-treated, n = 12, Placebo-treated, n = 10). Helminth infection induced a Th2-polarized cytokine response comprising elevated plasma IL-5 and parasite-specific IL-4, IL-5 and IL-13, and a global shift in the profile of systemic cytokine responses. Infection also elicited high levels of the regulatory cytokine IL-10 in response to T. suis antigens. Despite increased production of T. suis-specific cytokines in T. suis ova-treated participants, allergen-specific cytokine responses during the grass pollen season and the global profile of PBMC cytokine responses were not affected by T. suis ova treatment. This study suggests that cytokines induced by Trichuris suis ova treatment do not alter allergic reactivity to pollen during the peak of allergic rhinitis symptoms. © 2012 Blackwell Publishing Ltd.

Cytokine synthesis in occupational allergy to caddisflies in hydroelectric plant workers.

PubMed

Warrington, R J; Whitman, C; McPhillips Warrington, S

2003-10-01

Workers in hydroelectric plants appear to be readily sensitized to caddisfly allergens. This sensitization probably occurs de novo from occupational exposure. In some workers, sensitization occurs on a non-atopic background. Cytokine synthesis of IFN-gamma, IL-5 and IL-13 in atopic and non-atopic caddisfly-allergic workers was examined to determine if responses were similar or different. Peripheral blood mononuclear cells were isolated from atopic caddisfly-allergic workers, non-atopic caddisfly-allergic workers and non-atopic caddisfly-exposed but non-allergic workers. Stimulation with caddisfly antigens was carried out and synthesis of IFN-gamma, IL-5 and IL-13 was determined by sandwich ELISA. Both caddisfly-allergic and non-allergic subjects responded to stimulation with caddisfly extract. The response in non-atopic caddisfly-non-allergic subjects was TH1 predominant, while that in atopic caddisfly-allergic subjects was TH2 predominant. The response in non-atopic caddisfly-allergic subjects was between that of the atopic caddisfly-allergic workers and the non-atopic caddisfly-non-allergic workers and the trend was to a TH2 response. Work-related symptoms were similarly intermediate between the atopic caddisfly-allergic and non-atopic caddisfly-non-allergic group. Differences were significant for IFN-gamma/IL-5 ratios but not IFN-gamma/IL-13 ratios for atopic and non-atopic caddisfly-allergic individuals, compared to non-atopic caddisfly-non-allergic workers. However, a linear relationship existed between IFN-gamma synthesis and IL-5 and IL-13 synthesis in non-atopic caddisfly-allergic workers but not in atopic caddisfly-allergic subjects. Caddisfly allergy in hydroelectric workers may be a useful model for the development of allergy to a previously unencountered allergen, and points to some interesting differences between atopic and non-atopic subjects who become sensitized to environmental allergens. Copyright 2003 S. Karger AG, Basel

miR-122-SOCS1-JAK2 axis regulates allergic inflammation and allergic inflammation-promoted cellular interactions

PubMed Central

Kim, Hanearl; Kim, Hyuna; Byun, Jaehwan; Park, Yeongseo; Lee, Hansoo; Lee, Yun Sil; Choe, Jongseon; Kim, Young Myeong; Jeoung, Dooil

2017-01-01

The regulatory role of suppressor of cytokine signaling 1 (SOCS1) in inflammation has been reported. However, its role in allergic inflammation has not been previously reported. SOCS1 mediated in vitro and in vivo allergic inflammation. Histone deacetylase-3 (HDAC3), a mediator of allergic inflammation, interacted with SOCS1, and miR-384 inhibitor, a positive regulator of HDAC3, induced features of allergic inflammation in an SOCS1-dependent manner. miRNA array analysis showed that the expression of miR-122 was decreased by antigen-stimulation. TargetScan analysis predicted the binding of miR-122 to the 3′-UTR of SOCS1. miR-122 inhibitor induced in vitro and in vivo allergic features in SOCS1-dependent manner. SOCS1 was necessary for allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells. SOCS1 and miR-122 regulated cellular interactions involving cancer cells, mast cells and macrophages during allergic inflammation. SOCS1 mimetic peptide, D-T-H-F-R-T-F-R-S-H-S-D-Y-R-R-I, inhibited in vitro and in vivo allergic inflammation, allergic inflammation-promoted enhanced tumorigenic and metastatic potential of cancer cells, and cellular interactions during allergic inflammation. Janus kinase 2 (JAK2) exhibited binding to SOCS1 mimetic peptide and mediated allergic inflammation. Transforming growth factor- Δ1 (TGF-Δ1) was decreased during allergic inflammation and showed an anti-allergic effect. SOCS1 and JAK2 regulated the production of anti-allergic TGF-Δ1. Taken together, our results show that miR-122-SOCS1 feedback loop can be employed as a target for the development of anti-allergic and anti-cancer drugs. PMID:28968979

X-Ray based Lung Function measurement-a sensitive technique to quantify lung function in allergic airway inflammation mouse models

NASA Astrophysics Data System (ADS)

Dullin, C.; Markus, M. A.; Larsson, E.; Tromba, G.; Hülsmann, S.; Alves, F.

2016-11-01

In mice, along with the assessment of eosinophils, lung function measurements, most commonly carried out by plethysmography, are essential to monitor the course of allergic airway inflammation, to examine therapy efficacy and to correlate animal with patient data. To date, plethysmography techniques either use intubation and/or restraining of the mice and are thus invasive, or are limited in their sensitivity. We present a novel unrestrained lung function method based on low-dose planar cinematic x-ray imaging (X-Ray Lung Function, XLF) and demonstrate its performance in monitoring OVA induced experimental allergic airway inflammation in mice and an improved assessment of the efficacy of the common treatment dexamethasone. We further show that XLF is more sensitive than unrestrained whole body plethysmography (UWBP) and that conventional broncho-alveolar lavage and histology provide only limited information of the efficacy of a treatment when compared to XLF. Our results highlight the fact that a multi-parametric imaging approach as delivered by XLF is needed to address the combined cellular, anatomical and functional effects that occur during the course of asthma and in response to therapy.

STUDIES ON THE MECHANISM OF THE FORMATION OF THE PENICILLIN ANTIGEN

PubMed Central

Levine, Bernard B.

1960-01-01

Seven highly purified degradation products of penicillin G (PG) were examined with regard to their ability to cross-react allergically with PG. Guinea pig allergic contact dermatitis was employed as the test system. Three of these degradation products, D-benzylpenicillenic acid (BPE), D-penicillamine, and D-α-benzylpenicilloic acid were found to cross-react with PG and also to be capable of inducing delayed contact allergy in the guinea pig. BPE and PG cross-reacted with particularly intense reactions, and other immunologic experiments indicated that PG and BPE introduce identical allergic determinant groups into epidermal proteins. These experimental results were correlated with the results of previous studies concerning the degradation pathways of PG under physiological conditions in vitro, and the chemical reactivities of these degradation products. Based on these immunologic and chemical data, a schema is proposed which suggests the chemical pathways by which PG may react with epidermal proteins in vivo to form the penicillin antigen. The identity of the specific antigenic determinant groups of the penicillin antigen is suggested. The relationship between PG allergy of the contact dermatitis type in the guinea pig and PG allergy of the immediate type in man is discussed. PMID:13761469

Immune reactions and allergy in experimental anisakiasis

PubMed Central

Lee, Haneul Nari

2006-01-01

The third-stage larvae (L3) of the parasitic nematode, Anisakis simplex, have been implicated in the induction of hyperimmune allergic reactions in orally infected humans. In this work, we have conducted a review of an investigation into immune reactions occurring in animals experimentally infected with A. simplex L3. The patterns of serum antibody productions in the experimental animals against excretory-secretory products (ESP) of A. simplex L3 contributed to our current knowledge regarding specific humoral immune reactions in humans. In our review, we were able to determine that L3 infection of experimental animals may constitute a good model system for further exploration of immune mechanisms and allergy in anisakiasis of humans. PMID:17170569

γ-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates

PubMed Central

Abdala-Valencia, Hiam; Soveg, Frank

2016-01-01

γ-Tocopherol increases responses to allergen challenge in allergic adult mice, but it is not known whether γ-tocopherol regulates the development of allergic disease. Development of allergic disease often occurs early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. Therefore, we determined whether γ-tocopherol augments development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with γ-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to allergen challenge. The γ-tocopherol supplementation of allergic female mice increased the numbers of eosinophils twofold in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also about a twofold increase in pup lung CD11b+ subsets of CD11c+ dendritic cells and in numbers of these dendritic cells expressing the transcription factor IRF4. There was no change in several CD11b− dendritic cell subsets. Furthermore, maternal supplementation with γ-tocopherol increased the number of fetal liver CD11b+CD11c+ dendritic cells twofold in utero. In the pups, γ-tocopherol increased lung expression of the inflammatory mediators CCL11, amphiregulin, activin A, and IL-5. In conclusion, maternal supplementation with γ-tocopherol increased fetal development of subsets of dendritic cells that are critical for allergic responses and increased development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with γ-tocopherol in prenatal vitamins. PMID:26801566

Association between allergic disease, sleep-disordered breathing, and childhood nocturnal enuresis: a population-based case-control study.

PubMed

Tsai, Jeng-Dau; Chen, Hsuan-Ju; Ku, Min-Sho; Chen, Shan-Ming; Hsu, Chih-Chuan; Tung, Min-Che; Lin, Che-Chen; Chang, Hsing-Yi; Sheu, Ji-Nan

2017-12-01

Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present.

Epidemiology of allergic conjunctivitis: clinical appearance and treatment patterns in a population-based study.

PubMed

Leonardi, Andrea; Castegnaro, Angela; Valerio, Alvise La Gloria; Lazzarini, Daniela

2015-10-01

To analyse the most recently published studies on the prevalence of allergic conjunctivitis alone or in association with allergic rhinitis, and the clinical and demographic aspects of the disease. Allergic conjunctivitis or conjunctival symptoms are present in 30-71% of patients with allergic rhinitis. Allergic conjunctivitis alone has been estimated in 6-30% of the general population and in up to 30% in children alone or in association with allergic rhinitis. Seasonal allergic conjunctivitis is the most frequent form; however, studies from tertiary, ophthalmology referral centers report that the chronic forms, such as vernal and atopic keratoconjunctivitis, are the most frequently seen by ophthalmologists. A recent large survey performed at a national level involving 304 ophthalmologists showed that the majority of patients with allergic conjunctivitis suffer annually of few episodes of mild ,intermittent conjunctivitis. However, 30% of patients are affected by frequent episodes with intense and persistent symptoms. Treatment is frequently not appropriate. Even though allergic conjunctivitis is often associated to allergic rhinitis, epidemiology studies frequently do not include specific ophthalmological evaluations. An understanding of allergic conjunctivitis disease, its prevalence, demographics and treatment paradigms will provide important information towards understanding its pharmacoeconomics and burden on the national health systems.

Allergic Diseases and Internalizing Behaviors in Early Childhood

PubMed Central

LeMasters, Grace K.; Levin, Linda; Rothenberg, Marc E.; Assa'ad, Amal H.; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E.; Ryan, Patrick H.

2016-01-01

BACKGROUND AND OBJECTIVES: The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. METHODS: Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. RESULTS: The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8–5.8), anxiety (aOR: 2.0; 95% CI: 1.2–3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7–6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2–6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7–7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0–9.2) at age 4 had dose-dependent associations with internalizing scores. CONCLUSIONS: Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. PMID:26715608

Allergic Diseases and Internalizing Behaviors in Early Childhood.

PubMed

Nanda, Maya K; LeMasters, Grace K; Levin, Linda; Rothenberg, Marc E; Assa'ad, Amal H; Newman, Nicholas; Bernstein, David; Khurana-Hershey, Gurjit; Lockey, James E; Ryan, Patrick H

2016-01-01

The relationship between allergic diseases and internalizing disorders has not been well characterized with regard to multiple allergic diseases or longitudinal study. The objective of this study was to examine the association between multiple allergic diseases in early childhood with validated measures of internalizing disorders in the school-age years. Children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study underwent skin testing and examinations at ages 1, 2, 3, 4, and 7 years. At age 7, parents completed the Behavior Assessment System for Children, Second Edition (BASC-2), a validated measure of childhood behavior and emotion. The association between allergic diseases at age 4, including allergic rhinitis, allergic persistent wheezing, atopic dermatitis, and allergic sensitization, and BASC-2 internalizing, anxiety, and depression T scores at age 7 was examined by logistic and linear regression, adjusting for covariates. The cohort included 546 children with complete information on allergic disease and BASC-2 outcomes. Allergic rhinitis at age 4 was significantly associated with elevated internalizing (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.8-5.8), anxiety (aOR: 2.0; 95% CI: 1.2-3.6), and depressive scores (aOR: 3.2; 95% CI: 1.7-6.5) at age 7. Allergic persistent wheezing was significantly associated with elevated internalizing scores (aOR: 2.7; 95% CI: 1.2-6.3). The presence of >1 allergic disease (aOR: 3.6; 95% CI: 1.7-7.6) and allergic rhinitis with comorbid allergic disease(s) (aOR: 4.3; 95% CI: 2.0-9.2) at age 4 had dose-dependent associations with internalizing scores. Children with allergic rhinitis and allergic persistent wheezing at age 4 are at increased risk of internalizing behaviors at age 7. Furthermore, multiple allergic diseases had a dose-dependent association with elevated internalizing scores. Copyright © 2016 by the American Academy of Pediatrics.

Difference in the breast milk proteome between allergic and non-allergic mothers.

PubMed

Hettinga, Kasper A; Reina, Fabiola M; Boeren, Sjef; Zhang, Lina; Koppelman, Gerard H; Postma, Dirkje S; Vervoort, Jacques J M; Wijga, Alet H

2015-01-01

Breastfeeding has been linked to a reduction in the prevalence of allergy and asthma. However, studies on this relationship vary in outcome, which may partly be related to differences in breast milk composition. In particular breast milk composition may differ between allergic and non-allergic mothers. Important components that may be involved are breast milk proteins, as these are known to regulate immune development in the newborn. The objective of this study was therefore to explore differences in the proteins of breast milk from 20 allergic and non-allergic mothers. The results from this comparison may then be used to generate hypotheses on proteins associated with allergy in their offspring. Milk samples from allergic and non-allergic mothers were obtained from the PIAMA project, a prospective birth cohort study on incidence, risk factors, and prevention of asthma and inhalant allergy. Non-targeted proteomics technology, based on liquid chromatography and mass spectrometry, was used to compare breast milk from allergic and non-allergic mothers. Nineteen proteins, out of a total of 364 proteins identified in both groups, differed significantly in concentration between the breast milk of allergic and non-allergic mothers. Protease inhibitors and apolipoproteins were present in much higher concentrations in breast milk of allergic than non-allergic mothers. These proteins have been suggested to be linked to allergy and asthma. The non-targeted milk proteomic analysis employed has provided new targets for future studies on the relation between breast milk composition and allergy.

Climate change and occupational allergies: an overview on biological pollution, exposure and prevention.

PubMed

D'Ovidio, Maria Concetta; Annesi-Maesano, Isabella; D'Amato, Gennaro; Cecchi, Lorenzo

2016-01-01

Climate change, air pollution, temperature increase and other environmental variables are modifying air quality, contributing to the increase of prevalence of allergic respiratory diseases. Allergies are complex diseases characterized by multilevel interactions between individual susceptibility, response to immune modulation and environmental exposures to physical, chemical and biological agents. Occupational allergies introduce a further complexity to these relationships by adding occupational exposure to both the indoor and outdoor ones in the living environment. The aim of this paper is to overview climate-related allergy affecting environmental and occupational health, as literature data are scanty in this regard, and to suggest a management model of this risk based on a multidisciplinary approach, taking the case of biological pollution, with details on exposure and prevention. The management of climate-related occupational allergy should take into account preventive health strategies, environmental, public and occupational interventions, as well as to develop, implement, evaluate, and improve guidelines and standards protecting workers health under changing climatic conditions; new tools and strategies based on local conditions will have to be developed. Experimental studies and acquisition of environmental and personal data have to be matched to derive useful information for the scope of occupational health and safety.

Eosinophils: The unsung heroes in cancer?

PubMed

Varricchi, Gilda; Galdiero, Maria Rosaria; Loffredo, Stefania; Lucarini, Valeria; Marone, Giancarlo; Mattei, Fabrizio; Marone, Gianni; Schiavoni, Giovanna

2018-01-01

Prolonged low-grade inflammation or smoldering inflammation is a hallmark of a cancer. Eosinophils are components of the immune microenvironment that modulates tumor initiation and progression. Although canonically associated with a detrimental role in allergic disorders, these cells can induce a protective immune response against helminthes, viral and bacterial pathogens. Eosinophils are a source of anti-tumorigenic (e.g., TNF-α, granzyme, cationic proteins, and IL-18) and protumorigenic molecules (e.g., pro-angiogenic factors) depending on the milieu. In several neoplasias (e.g., melanoma, gastric, colorectal, oral and prostate cancer) eosinophils play an anti-tumorigenic role, in others (e.g., Hodgkin's lymphoma, cervical carcinoma) have been linked to poor prognosis, whereas in yet others they are apparently innocent bystanders. These seemingly conflicting results suggest that the role of eosinophils and their mediators could be cancer-dependent. The microlocalization (e.g., peritumoral vs intratumoral) of eosinophils could be another important aspect in the initiation/progression of solid and hematological tumors. Increasing evidence in experimental models indicates that activation/recruitment of eosinophils could represent a new therapeutic strategy for certain tumors (e.g., melanoma). Many unanswered questions should be addressed before we understand whether eosinophils are an ally, adversary or neutral bystanders in different types of human cancers.

The split personality of NKT cells in malignancy, autoimmune and allergic disorders

PubMed Central

Subleski, Jeff J; Jiang, Qun; Weiss, Jonathan M; Wiltrout, Robert H

2011-01-01

NKT cells are a heterogeneous subset of specialized, self-reactive T cells, with innate and adaptive immune properties, which allow them to bridge innate and adaptive immunity and profoundly influence autoimmune and malignant disease outcomes. NKT cells mediate these activities through their ability to rapidly express pro- and anti-inflammatory cytokines that influence the type and magnitude of the immune response. Not only do NKT cells regulate the functions of other cell types, but experimental evidence has found NKT cell subsets can modulate the functions of other NKT subsets. Depending on underlying mechanisms, NKT cells can inhibit or exacerbate autoimmunity and malignancy, making them potential targets for disease intervention. NKT cells can respond to foreign and endogenous antigenic glycolipid signals that are expressed during pathogenic invasion or ongoing inflammation, respectively, allowing them to rapidly react to and influence a broad array of diseases. In this article we review the unique development and activation pathways of NKT cells and focus on how these attributes augment or exacerbate autoimmune disorders and malignancy. We also examine the growing evidence that NKT cells are involved in liver inflammatory conditions that can contribute to the development of malignancy. PMID:21995570

Flavonoids and Asthma

PubMed Central

Tanaka, Toshio; Takahashi, Ryo

2013-01-01

Asthma is a chronic disease, characterized by airway inflammation, airflow limitation, hyper-reactivity and airway remodeling. It is believed that asthma is caused by the interaction between genetic and environmental factors. The prevalence of allergic diseases, including asthma, has increased worldwide during the past two decades. Although the precise reasons that have caused this increase remain unknown, dietary change is thought to be one of the environmental factors. Flavonoids, which are polyphenolic plant secondary metabolites ubiquitously present in vegetables, fruits and beverages, possess antioxidant and anti-allergic traits, as well as immune-modulating activities. Flavonoids are powerful antioxidants and anti-allergic nutrients that inhibit the release of chemical mediators, synthesis of Th2 type cytokines, such as interleukin (IL)-4 and IL-13, and CD40 ligand expression by high-affinity immunoglobulin E (IgE) receptor-expressing cells, such as mast cells and basophils. They also inhibit IL-4-induced signal transduction and affect the differentiation of naïve CD4+ T cells into effector T-cells through their inhibitory effect on the activation of the aryl hydrocarbon receptor. Various studies of flavonoids in asthmatic animal models have demonstrated their beneficial effects. The results of several epidemiological studies suggest that an increase in flavonoid intake is beneficial for asthma. Moreover, clinical trials of flavonoids have shown their ameliorative effects on symptoms related to asthma. However, these human studies are currently limited; further validation is required to clarify whether an appropriate intake of flavonoids may constitute dietary treatment and for part of a preventive strategy for asthma. PMID:23752494

Reconstitution of the human biome as the most reasonable solution for epidemics of allergic and autoimmune diseases.

PubMed

Bilbo, Staci D; Wray, Gregory A; Perkins, Sarah E; Parker, William

2011-10-01

A wide range of hyperimmune-associated diseases plague post-industrial society, with a prevalence and impact that is staggering. Strong evidence points towards a loss of helminths from the ecosystem of the human body (the human biome) as the most important factor in this epidemic. Helminths, intestinal worms which are largely eradicated by elements of post-industrial culture including toilets and water treatment facilities, have an otherwise ubiquitous presence in vertebrates, and have co-evolved with the immune system. Not only do helminths discourage allergic and autoimmune reactions by diverting the immune system away from these pathologic processes and stimulating host regulatory networks, helminths release a variety of factors which down-modulate the immune system. A comprehensive view of hyperimmune-related disease based on studies in immunology, parasitology, evolutionary biology, epidemiology, and neurobiology indicates that the effects of biome depletion may not yet be fully realized, and may have an unexpectedly broad impact on many areas of human biology, including cognition. Fortunately, colonization with helminths results in a cure of numerous autoimmune and allergic diseases in laboratory rodents, and clinical studies in humans have indicated their utility for treatment of both multiple sclerosis and inflammatory bowel disease. Based on these considerations, commitment of considerable resources toward understanding the effects of "biome depletion" and systematically evaluating the most effective approach toward biome reconstitution is strongly encouraged. Copyright © 2011 Elsevier Ltd. All rights reserved.

Treatment of Allergic Rhinitis Is Associated with Improved Attention Performance in Children: The Allergic Rhinitis Cohort Study for Kids (ARCO-Kids)

PubMed Central

Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Kim, Jeong-Whun

2014-01-01

Background It has been well known that pediatric allergic rhinitis was associated with poor performance at school due to attention deficit. However, there were no cohort studies for the effect of treatment of allergic rhinitis on attention performance in pediatric population. Thus, the aim of this study was to investigate whether attention performance was improved after treatment in children with allergic rhinitis. Methods In this ARCO-Kids (Allergic Rhinitis Cohort Study for Kids), consecutive pediatric patients with rhinitis symptoms underwent a skin prick test and computerized comprehensive attention test. According to the skin prick test results, the children were diagnosed as allergic rhinitis or non- allergic rhinitis. All of the patients were regularly followed up and treated with oral medication or intranasal corticosteroid sprays. The comprehensive attention tests consisted of sustained and divided attention tasks. Each of the tasks was assessed by the attention score which was calculated by the number of omission and commission errors. The comprehension attention test was repeated after 1 year. Results A total of 797 children with allergic rhinitis and 239 children with non-allergic rhinitis were included. Initially, the attention scores of omission and commission errors on divided attention task were significantly lower in children with allergic rhinitis than in children with non-allergic rhinitis. After 1 year of treatment, children with allergic rhinitis showed improvement in attention: commission error of sustained (95.6±17.0 vs 97.0±16.6) and divided attention task (99.1±15.8 vs 91.8±23.5). Meanwhile, there was no significant difference of attention scores in children with non-allergic rhinitis. Conclusions Our study showed that management of allergic rhinitis might be associated with improvement of attention. PMID:25330316

Platelet–Eosinophil Interactions As a Potential Therapeutic Target in Allergic Inflammation and Asthma

PubMed Central

Shah, Sajeel A.; Page, Clive P.; Pitchford, Simon C.

2017-01-01

The importance of platelet activation during hemostasis is well understood. An understanding of these mechanisms has led to the use of several classes of anti-platelet drugs to inhibit aggregation for the prevention of thrombi during cardiovascular disease. It is now also recognized that platelets can function very differently during inflammation, as part of their role in the innate immune response against pathogens. This dichotomy in platelet function occurs through distinct physiological processes and alternative signaling pathways compared to that of hemostasis (leading to platelet aggregation) and is manifested as increased rheological interactions with leukocytes, the ability to undergo chemotaxis, communication with antigen-presenting cells, and direct anti-pathogen responses. Mounting evidence suggests platelets are also critical in the pathogenesis of allergic diseases such as asthma, where they have been associated with antigen presentation, bronchoconstriction, bronchial hyperresponsiveness, airway inflammation, and airway remodeling in both clinical and experimental studies. In particular, platelets have been reported bound to eosinophils in the blood of patients with asthma and the incidence of these events increases after both spontaneous asthma attacks in a biphasic manner, or after allergen challenge in the clinic. Platelet depletion in animal models of allergic airway inflammation causes a profound reduction in eosinophil recruitment to the lung, suggesting that the association of platelets with eosinophils is indeed an important event during eosinophil activation. Furthermore, in cases of severe asthma, and in animal models of allergic airways inflammation, platelet–eosinophil complexes move into the lung through a platelet P-selectin-mediated, eosinophil β1-integrin activation-dependent process, while platelets increase adherence of eosinophils to the vascular endothelium in vitro, demonstrating a clear interaction between these cell types in allergic inflammatory diseases. This review will explore non-thrombotic platelet activation in the context of allergy and the association of platelets with eosinophils, to reveal how these phenomena may lead to the discovery of novel therapeutic targets. PMID:28848732

Protease-Activated Receptor-2 Activation Contributes to House Dust Mite-Induced IgE Responses in Mice

PubMed Central

Post, Sijranke; Heijink, Irene H.; Petersen, Arjen H.; de Bruin, Harold G.; van Oosterhout, Antoon J. M.; Nawijn, Martijn C.

2014-01-01

Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium, thereby potentially inducing allergic sensitization at the expense of inhalation tolerance. We hypothesized that the proteolytic activity of allergens may play an important factor in the allergenicity to house dust mite and is essential to overcome airway tolerance. Here, we aimed to investigate the role of PAR-2 activation in allergic sensitization and HDM-induced allergic airway inflammation. In our study, Par-2 deficient mice were treated with two different HDM extracts containing high and low serine protease activities twice a week for a period of 5 weeks. We determined airway inflammation through quantification of percentages of mononuclear cells, eosinophils and neutrophils in the bronchial alveolar lavage fluid and measured total IgE and HDM-specific IgE and IgG1 levels in serum. Furthermore, Th2 and pro-inflammatory cytokines including IL-5, IL-13, Eotaxin-1, IL-17, KC, Chemokine (C-C motif) ligand 17 (CCL17) and thymic stromal lymphopoietin (TSLP), were measured in lung tissue homogenates. We observed that independent of the serine protease content, HDM was able to induce elevated levels of eosinophils and neutrophils in the airways of both wild-type (WT) and Par-2 deficient mice. Furthermore, we show that induction of pro-inflammatory cytokines by HDM exposure is independent of Par-2 activation. In contrast, serine protease activity of HDM does contribute to enhanced levels of total IgE, but not HDM-specific IgE. We conclude that, while Par-2 activation contributes to the development of IgE responses, it is largely dispensable for the HDM-induced induction of pro-inflammatory cytokines and airway inflammation in an experimental mouse model of HDM-driven allergic airway disease. PMID:24651123

Pharmacokinetics and Differential Regulation of Cytochrome P450 Enzymes in Type 1 Allergic Mice.

PubMed

Tanino, Tadatoshi; Komada, Akira; Ueda, Koji; Bando, Toru; Nojiri, Yukie; Ueda, Yukari; Sakurai, Eiichi

2016-12-01

Type 1 allergic diseases are characterized by elevated production of specific immunoglobulin E (IgE) for each antigen and have become a significant health problem worldwide. This study investigated the effect of IgE-mediated allergy on drug pharmacokinetics. To further understand differential suppression of hepatic cytochrome P450 (P450) activity, we examined the inhibitory effect of nitric oxide (NO), a marker of allergic conditions. Seven days after primary sensitization (PS7) or secondary sensitization (SS7), hepatic CYP1A2, CYP2C, CYP2E1, and CYP3A activities were decreased to 45%-75% of the corresponding control; however, CYP2D activity was not downregulated. PS7 and SS7 did not change the expression levels of five P450 proteins. Disappearance of CYP1A2 and CYP2D substrates from the plasma was not significantly different between allergic mice and control mice. In contrast, the area under the curve of a CYP1A2-mediated metabolite in PS7 and SS7 mice was reduced by 50% of control values. Total clearances of a CYP2E1 substrate in PS7 and SS7 mice were significantly decreased to 70% and 50% respectively, of the control without altering plasma protein binding. Hepatic amounts of CYP1A2 and CYP2E1 substrates were enhanced by allergic induction, being responsible for each downregulated activity. NO scavenger treatment completely improved the downregulated P450 activities. Therefore, our data suggest that the onset of IgE-mediated allergy alters the pharmacokinetics of major P450-metabolic capacity-limited drugs except for CYP2D drugs. NO is highly expected to participate in regulatory mechanisms of the four P450 isoforms. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Hepatic Flavin-Containing Monooxygenase 3 Enzyme Suppressed by Type 1 Allergy-Produced Nitric Oxide.

PubMed

Tanino, Tadatoshi; Bando, Toru; Komada, Akira; Nojiri, Yukie; Okada, Yuna; Ueda, Yukari; Sakurai, Eiichi

2017-11-01

Flavin-containing monooxygenases (FMOs) are major mammalian non-cytochrome P450 oxidative enzymes. T helper 2 cell-activated allergic diseases produce excess levels of nitric oxide (NO) that modify the functions of proteins. However, it remains unclear whether allergy-induced NO affects the pharmacokinetics of drugs metabolized by FMOs. This study investigated alterations of hepatic microsomal FMO1 and FMO3 activities in type 1 allergic mice and further examined the interaction of FMO1 and FMO3 with allergy-induced NO. Imipramine (IMP; FMO1 substrate) N- oxidation activity was not altered in allergic mice with high serum NO and immunoglobulin E levels. At 7 days after primary sensitization (PS7) or secondary sensitization (SS7), benzydamine (BDZ; FMO1 and FMO3 substrate) N- oxygenation was significantly decreased to 70% of individual controls. The expression levels of FMO1 and FMO3 proteins were not significantly changed in the sensitized mice. Hepatic inducible NO synthase (iNOS) mRNA level increased 5-fold and 15-fold in PS7 and SS7 mice, respectively, and hepatic tumor necrosis factor- α levels were greatly enhanced. When a selective iNOS inhibitor was injected into allergic mice, serum NO levels and BDZ N- oxygenation activity returned to control levels. NO directly suppressed BDZ N- oxygenation, which was probably related to FMO3-dependent metabolism in comparison with IMP N- oxidation. In hepatic microsomes from PS7 and SS7 mice, the suppression of BDZ N- oxygenation was restored by ascorbate. Therefore, type 1 allergic mice had differentially suppressed FMO3-dependent BDZ N- oxygenation. The suppression of FMO3 metabolism related to reversible S- nitrosyl modifications of iNOS-derived NO. NO is expected to alter FMO3-metabolic capacity-limited drug pharmacokinetics in humans. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won

Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct ofmore » humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune response and helminth infection.« less

Discovering susceptibility genes for allergic rhinitis and allergy using a genome-wide association study strategy.

PubMed

Li, Jingyun; Zhang, Yuan; Zhang, Luo

2015-02-01

Allergic rhinitis and allergy are complex conditions, in which both genetic and environmental factors contribute to the pathogenesis. Genome-wide association studies (GWASs) employing common single-nucleotide polymorphisms have accelerated the search for novel and interesting genes, and also confirmed the role of some previously described genes which may be involved in the cause of allergic rhinitis and allergy. The aim of this review is to provide an overview of the genetic basis of allergic rhinitis and the associated allergic phenotypes, with particular focus on GWASs. The last decade has been marked by the publication of more than 20 GWASs of allergic rhinitis and the associated allergic phenotypes. Allergic diseases and traits have been shown to share a large number of genetic susceptibility loci, of which IL33/IL1RL1, IL-13-RAD50 and C11orf30/LRRC32 appear to be important for more than two allergic phenotypes. GWASs have further reflected the genetic heterogeneity underlying allergic phenotypes. Large-scale genome-wide association strategies are underway to discover new susceptibility variants for allergic rhinitis and allergic phenotypes. Characterization of the underlying genetics provides us with an insight into the potential targets for future studies and the corresponding interventions.

A matched patient-sibling study on the usage of paracetamol and the subsequent development of allergy and asthma.

PubMed

Koniman, Riece; Chan, Yiong Huak; Tan, Teng Nging; Van Bever, Hugo P

2007-03-01

A number of studies have suggested that intake of paracetamol during pregnancy and during the first months of life is associated with an increased risk of childhood asthma. We aimed to determine the association between paracetamol usage during pregnancy and the first 6 months of life, and childhood allergy (i.e. positive skin prick tests), allergic asthma, and asthma, using a matched patient-sibling study comparing patients with allergic asthma with their healthy siblings without any symptoms of allergic diseases. Allergy in patients and their siblings was determined by skin prick tests. Children having at least one positive skin prick test were considered to be allergic. Intake of paracetamol was assessed by standardized, interviewer-administered, questionnaire. Nineteen pairs of allergic asthma patients vs. non-allergic siblings were compared to determine the risk factors for allergic asthma, while 15 pairs of allergic asthma patients vs. allergic siblings were compared to determine the risk factors for asthma. Moreover, 33 pairs of allergic asthma patients vs. non-asthmatic siblings (with and without allergy) were compared to determine the risk factors for asthma. In addition, 17 allergic siblings (without asthma) were compared with 19 non-allergic siblings (without asthma) to determine the risk factors for allergy. Usage of paracetamol during pregnancy was associated with allergic asthma (p = 0.03). Furthermore, usage of paracetamol between birth and 6 months of age, and between 4 and 6 months of age, was also found to be associated with non-allergic asthma (p = 0.008 and p = 0.03 respectively). Usage of paracetamol during pregnancy and during the early months of life may play a role in the development of allergic and non-allergic asthma in children. However, due to obvious ethical reasons, direct evidence for this association (i.e. a double-blind, prospective study) is not available.

Involvement of the iNKT Cell Pathway Is Associated With Early-Onset Eosinophilic Esophagitis and Response to Allergen Avoidance Therapy

PubMed Central

Lexmond, Willem S.; Neves, Joana F.; Nurko, Samuel; Olszak, Torsten; Exley, Mark A.; Blumberg, Richard S.; Fiebiger, Edda

2014-01-01

OBJECTIVES Recent experimental evidence suggests that environmental microbial factors early in life determine susceptibility to allergic diseases through inappropriate chemotaxis and local activation of CD1d-restricted, invariant chain natural killer T (iNKT) cells. In this study, we analyzed the involvement of these pathways in pediatric patients with eosinophilic esophagitis (EoE) before and after dietary allergen elimination. METHODS mRNA expression levels of components of the C-X-C motif chemokine ligand 16 (CXCL16)–iNKT–CD1d axis were compared in esophageal biopsies from EoE patients vs. normal or inflammatory controls and before and after treatment. RESULTS CXCL16, iNKT cell–associated cell marker Vα24, and CD1d were significantly upregulated in esophageal biopsies from EoE patients and correlated with the expression of inflammatory mediators associated with allergy. Upregulation of each of these factors was significantly more pronounced in patients aged < 6 years at diagnosis, and this early-onset EoE subpopulation was characterized by a more prominent food allergic disease phenotype in a cohort-wide analysis. Successful, but not unsuccessful, treatment of early-onset EoE patients with dietary elimination of instigating allergens led to reduction in infiltrating iNKT cells and complete normalization of mRNA expression levels of CXCL16 and CD1d. CONCLUSIONS Our observations place iNKT cells at the center of allergic inflammation associated with EoE, which could have profound implications for our understanding, treatment and prevention of this and other human allergic diseases. PMID:24513807

Parasitic Helminths: New Weapons against Immunological Disorders

PubMed Central

Osada, Yoshio; Kanazawa, Tamotsu

2010-01-01

The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis). Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology. PMID:20169100

Parasitic helminths: new weapons against immunological disorders.

PubMed

Osada, Yoshio; Kanazawa, Tamotsu

2010-01-01

The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis). Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology.

38 CFR 3.380 - Diseases of allergic etiology.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic manifestations...

38 CFR 3.380 - Diseases of allergic etiology.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic manifestations...

38 CFR 3.380 - Diseases of allergic etiology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic manifestations...

38 CFR 3.380 - Diseases of allergic etiology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic manifestations...

38 CFR 3.380 - Diseases of allergic etiology.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Diseases of allergic... Specific Diseases § 3.380 Diseases of allergic etiology. Diseases of allergic etiology, including bronchial... progress nor as due to the inherent nature of the disease. Seasonal and other acute allergic manifestations...

Allergic rhinitis and arterial blood pressure: a population-based study.

PubMed

Sakallioglu, O; Polat, C; Akyigit, A; Cetiner, H; Duzer, S

2018-05-01

To investigate the likelihood of allergic rhinitis and potential co-morbidities, and to assess whether allergic rhinitis is associated with arterial blood pressure and hypertension. In this population-based study, 369 adults with allergic rhinitis and asthma were assessed via a questionnaire and immunoglobulin E levels. There were four groups: control (n = 90), allergic rhinitis (n = 99), asthma (n = 87) and hypertension (n = 93). Arterial blood pressure was measured in all groups. There were no significant differences in systolic or diastolic blood pressure between males and females in any group. Pairwise comparisons revealed no significant differences between: the control and allergic rhinitis groups, the control and asthma groups, or the allergic rhinitis and asthma groups. The systolic and diastolic blood pressure values of males and females were significantly higher in the hypertension group than the allergic rhinitis group. There were no significant differences in systolic blood pressure or diastolic blood pressure for seasonal and perennial allergic rhinitis patients. Rhinitis was not associated with increased blood pressure. Allergic rhinitis can coincide with asthma and hypertension. The findings do not support the need for blood pressure follow up in allergic rhinitis patients.

Food and Natural Materials Target Mechanisms to Effectively Regulate Allergic Responses.

PubMed

Shin, Hee Soon; Shon, Dong-Hwa

2015-01-01

An immune hypersensitivity disorder called allergy is caused by diverse allergens entering the body via skin contact, injection, ingestion, and/or inhalation. These allergic responses may develop into allergic disorders, including inflammations such as atopic dermatitis, asthma, anaphylaxis, food allergies, and allergic rhinitis. Several drugs have been developed to treat these allergic disorders; however, long-term intake of these drugs could have adverse effects. As an alternative to these medicines, food and natural materials that ameliorate allergic disorder symptoms without producing any side effects can be consumed. Food and natural materials can effectively regulate successive allergic responses in an allergic chain-reaction mechanism in the following ways: [1] Inhibition of allergen permeation via paracellular diffusion into epithelial cells, [2] suppression of type 2 T-helper (Th) cell-related cytokine production by regulating Th1/Th2 balance, [3] inhibition of pathogenic effector CD4(+) T cell differentiation by inducing regulatory T cells (Treg), and [4] inhibition of degranulation in mast cells. The immunomodulatory effects of food and natural materials on each target mechanism were scientifically verified and shown to alleviate allergic disorder symptoms. Furthermore, consumption of certain food and natural materials such as fenugreek, skullcap, chitin/chitosan, and cheonggukjang as anti-allergics have merits such as safety (no adverse side effects), multiple suppressive effects (as a mixture would contain various components that are active against allergic responses), and ease of consumption when required. These merits and anti-allergic properties of food and natural materials help control various allergic disorders.

Effect of live attenuated vaccines on the course of experimental allergic encephalomyelitis. A pilot study.

PubMed

Caspary, E A

1977-01-01

The clinical severity of EAE is enhanced by pre-treatment with distemper, measles and BCG vaccine, measles vaccine gives a more severe onset of disease. Rubella vaccine and TAB leads to mild disease which recurs on re-treatment with the appropriate vaccine. These findings and their possible significance in MS are briefly discussed.

Thrombomodulin inhibits the activation of eosinophils and mast cells.

PubMed

Roeen, Ziaurahman; Toda, Masaaki; D'Alessandro-Gabazza, Corina N; Onishi, Masahiro; Kobayashi, Tetsu; Yasuma, Taro; Urawa, Masahito; Taguchi, Osamu; Gabazza, Esteban C

2015-01-01

Eosinophils and mast cells play critical roles in the pathogenesis of bronchial asthma. Activation of both cells leads to the release of pro-inflammatory mediators in the airway of asthmatic patients. Recently, we have shown that inhaled thrombomodulin inhibits allergic bronchial asthma in a mouse model. In the present study, we hypothesize that thrombomodulin can inhibit the activation of eosinophils and mast cells. The effect of thrombomodulin on the activation and release of inflammatory mediators from eosinophils and mast cells was evaluated. Thrombomodulin inhibited the eotaxin-induced chemotaxis, upregulation of CD11b and degranulation of eosinophils. Treatment with thrombomodulin also significantly suppressed the degranulation and synthesis of inflammatory cytokines and chemokines in eosinophils and mast cells. Mice treated with a low-dose of inhaled thrombomodulin have decreased number of eosinophils and activated mast cells and Th2 cytokines in the lungs compared to untreated mice. The results of this study suggest that thrombomodulin may modulate allergic responses by inhibiting the activation of both eosinophils and mast cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Phytochemicals to prevent inflammation and allergy.

PubMed

Bellik, Yuva; Hammoudi, Si M; Abdellah, Fatiha; Iguer-Ouada, Mokrane; Boukraâ, Laïd

2012-05-01

Recently, much interest has been generated for a wide range of phyto-constituents with reports demonstrating their role in the modulation of inflammatory responses, including phenolics, alkaloids, and terpenoids. Natural products have long been, over the years, contributed to the development of modern therapeutic drugs. At present, steroids, antihistaminic drugs, suppressants or inhibitors of the release of mediators and the like have been used as anti-allergic agents. However, some of them lack immediate effectiveness or have central side effects. Drug discovery from plants involves a multidisciplinary approach combining botanical, ethno-botanical, phytochemical and biological techniques. Several natural product drugs of plant origin are in clinical use and some are undergoing Phase II and Phase III clinical trials. A major effort was directed toward discovery of novel anti-inflammatory and anti-allergic agents, which resulted in the invention of several patented formulations. These formulations concern a variety of pharmaceutical preparations which can be used as solid or liquid dosage forms or encapsulated as a soft or hard gelatin capsule. The present article is a short review of recent patents on the role of phytochemicals in preventing inflammation and allergy.

Conduction block in the peripheral nervous system in experimental allergic encephalomyelitis

NASA Astrophysics Data System (ADS)

Pender, M. P.; Sears, T. A.

1982-04-01

Experimental allergic encephalomyelitis (EAE) has been widely studied as a model of multiple sclerosis, a central nervous system (CNS) disease of unknown aetiology. The clinical features of both EAE and multiple sclerosis provide the only guide to the progress and severity of these diseases, and are used to assess the response to treatment. In such comparisons the clinical features of EAE are assumed to be due to lesions in the CNS, but in this disease there is also histological evidence of damage to the peripheral nervous system1-8. However, the functional consequences of such peripheral lesions have been entirely ignored. To examine this we have studied nerve conduction in rabbits with EAE. We report here that most of the large diameter afferent fibres are blocked in the region of the dorsal root ganglion and at the dorsal root entry zone, thus accounting for the loss of tendon jerks and also, through the severe loss of proprioceptive information, the ataxia of these animals. We conclude that whenever clinical comparisons are made between EAE and multiple sclerosis, the pathophysiology associated with the histological damage of the peripheral nervous system must be taken into account.

The role of myelin lipids in experimental allergic encephalomyelitis. Part 1. Influence on disease production by non-encephalitogenic doses of myelin basic protein.

PubMed

Hosein, Z Z; Gilbert, J J; Strejan, G H

1984-12-01

Hartley guinea pig central nervous system (CNS) myelin has been purified and fractionated into its protein and lipid components. Experimental allergic encephalomyelitis (EAE) was induced in juvenile strain 13 guinea pigs with both lyophilized and fresh 'wet' myelin. However, a larger dose of lyophilized myelin was required to induce chronic EAE. Total myelin lipids, galactocerebrosides, gangliosides, phospholipids or proteolipids were combined with a non-encephalitogenic dose of myelin basic protein (MBP) and injected in juvenile Hartley guinea pigs. No clinical or histological manifestations of disease were observed. Parameters of immune functions indicated that the total myelin lipids augmented cell-mediated immune responses as measured by in vitro lymphocyte transformation and by a significant decrease in the percentage of peripheral early T cells. Only the proteolipids elicited delayed hypersensitivity reactions. Animals that received the phospholipid-MBP combination showed no changes when compared to animals injected with MBP alone. The results suggest that although the myelin lipids did not act synergistically with a non-encephalitogenic dose of MBP to induce EAE, they induced immunological changes and potentiated the immune response to MBP.

The association between the parenting stress of the mother and the incidence of allergic rhinitis in their children.

PubMed

Kim, Min Bum; Kim, Jeong Hong; Lee, Keun-Hwa; Hong, Seong-Chul; Lee, Hye-Sook; Kang, Ju Wan

2017-10-01

The prevalence of allergic rhinitis and the social burden related to the management of allergic rhinitis have persistently increased. There are many studies investigating the association between the allergic diseases of children and the stress of their parent. However, the relationship between parenting stress and the incidence of allergic rhinitis among children requires further investigation. We aimed to investigate the significance of parenting stress for mothers with children treated for allergic rhinitis. The mothers of 250 children in the second and third grade of elementary school were involved in this study. The Parenting Stress Index-Short Form (PSI-SF) was used to measure parenting stress. Additionally, the monthly household income, treatment history for allergic diseases (atopic dermatitis, asthma, and allergic rhinitis) during the past 12 months, and maternal education status were investigated using the questionnaire. Parenting stress index score was significantly higher among the mothers of children treated for allergic rhinitis (76.41 ± 9.35) compared with the parents of children without treatment history for allergic rhinitis (70.06 ± 13.74). Nonetheless, there were no significant differences between the cases of children with atopic dermatitis and those with asthma. We analyzed the association between allergic rhinitis and parenting stress adjusted for the monthly household income, and maternal education status, and showed that a treatment history of allergic rhinitis was significantly associated with parenting stress (coefficient 7.477, 95% interval 1.703-13.252; p = 0.011). Treatment of the children for allergic rhinitis significantly affects the parenting stress of their mother. We recommend that mothers with children with allergic rhinitis should receive appropriate counseling about parenting stress. Copyright © 2017 Elsevier B.V. All rights reserved.

Bee sting allergy in beekeepers.

PubMed

Eich-Wanger, C; Müller, U R

1998-10-01

Beekeepers are strongly exposed to honey bee stings and therefore at an increased risk to develop IgE-mediated allergy to bee venom. We wondered whether bee venom-allergic beekeepers were different from normally exposed bee venom-allergic patients with regard to clinical and immunological parameters as well as their response to venom immunotherapy. Among the 459 bee venom-allergic patients seen over the 5 year period 1987-91, 62 (14%) were beekeepers and 44 (10%) family members of beekeepers. These two groups were compared with 101 normally exposed bee venom-allergic patients matched with the allergic beekeepers for age and sex, regarding clinical parameters, skin sensitivity, specific IgE and IgG antibodies to bee venom as well as safety and efficacy of venom immunotherapy. As expected, allergic beekeepers had been stung most frequently before the first allergic reaction. The three groups showed a similar severity of allergic symptoms following bee stings and had an equal incidence of atopic diseases. Allergic beekeepers showed higher levels of bee venom-specific serum IgG, lower skin sensitivity and lower levels of bee venom specific serum IgE than bee venom-allergic control patients. A negative correlation between number of stings and skin sensitivity as well as specific IgE was found in allergic beekeepers and their family members, while the number of stings was positively correlated with specific IgG in these two groups. Venom immunotherapy was equally effective in the three groups, but better tolerated by allergic beekeepers than the two other groups. The majority of allergic beekeepers continued bee-keeping successfully under the protection of venom immunotherapy. The lower level of sensitivity in diagnostic tests and the better tolerance of immunotherapy in allergic beekeepers is most likely related to the high level of specific IgG in this group.

Purified Timothy grass pollen major allergen Phl p 1 may contribute to the modulation of allergic responses through a pleiotropic induction of cytokines and chemokines from airway epithelial cells.

PubMed

Röschmann, K I L; van Kuijen, A-M; Luiten, S; Jonker, M J; Breit, T M; Fokkens, W J; Petersen, A; van Drunen, C M

2012-03-01

By definition, allergens are proteins with the ability to elicit powerful T helper lymphocyte type 2 (Th2) responses, culminating in immunoglobulin (Ig)E antibody production. Why specific proteins cause aberrant immune responses has remained largely unanswered. Recent data suggest that there may be several molecular paths that may affect allergenicity of proteins. The focus of this study is the response of airway epithelium to a major allergen from Phleum pratense Phl p 1. Instead of focusing on a few genes and proteins that might be affected by the major allergen, our aim was to obtain a broader view on the immune stimulatory capacity of Phl p 1. We therefore performed detailed analysis on mRNA and protein level by using a microarray approach to define Phl p 1-induced gene expression. We found that this allergen induces modulation and release of a broad range of mediators, indicating it to be a powerful trigger of the immune system. We were able to show that genes belonging to the GO cluster 'cell communication' were among the most prominent functional groups, which is also reflected in cytokines and chemokines building centres in a computational model of direct gene interaction. Further detailed comparison of grass pollen extract (GPE)- and Phl p 1-induced gene expression might be beneficial with regard to the application of single components within diagnosis and immunotherapy. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Allergic rhinitis

MedlinePlus

... allergic to, such as dust, animal dander, or pollen. Symptoms can also occur when you eat a ... article focuses on allergic rhinitis due to plant pollens. This type of allergic rhinitis is commonly called ...

Role of Skin Prick Test in Allergic Disorders: A Prospective Study in Kashmiri Population in Light of Review

PubMed Central

Rasool, Roohi; Shera, Irfan Ali; Nissar, Saniya; Shah, Zaffar A; Nayak, Niyaz; Siddiqi, Mushtaq A; Sameer, Aga Syed

2013-01-01

Background: Skin prick test (SPT) is the most effective diagnostic test to detect IgE mediated type I allergic reactions like allergic rhinitis, atopic asthma, acute urticaria, food allergy etc. SPTs are done to know allergic sensitivity and applied for devising immunotherapy as the therapeutic modality. Materials and Methods: This prospective study was conducted in the department of Immunology and Molecular medicine at SKIMS. A total of 400 patients suffering from allergic rhinitis, asthma and urticaria were recruited in this study. SPT was performed with panel of allergens including house dust mite, pollens, fungi, dusts, cockroach, sheep wool and dog epithelia. Allergen immunotherapy was given to allergic rhinitis and asthmatic patients as therapeutic modality. Results: In our study, age of patients ranged from 6 to 65 years. Majority of patients were in the age group of 20-30 years (72%) with Male to female ratio of 1:1.5. Of the 400 patients, 248 (62%) had urticaria, 108 (27%) patients had allergic rhinitis and 44 (11%) patients had asthma. SPT reaction was positive in 38 (86.4%) with allergic asthma, 74 (68.5%) patients with allergic rhinitis and 4 (1.6%) patient with urticaria, respectively. Allergen immunotherapy was effective in 58% patients with allergic rhinitis and 42% allergic asthma. Conclusion: Identifiable aeroallergen could be detected in 86.4% allergic asthma and 68.5% allergic rhinitis patients by SPT alone. Pollens were the most prevalent causative allergen. There was significant relief in the severity of symptoms, medication intake with the help of allergen immunotherapy. PMID:23372205

Cytokine profile of food-allergic post-liver transplant children is identified by high levels of IL-5 and low IL-10 secretion from patients' peripheral blood mononuclear cells.

PubMed

Nahum, Amit; Brener, Avivit; Granot, Ettie

2015-11-01

Severe allergic reaction to food following liver transplantation is a well-known phenomenon. However, the mechanisms underlying this phenomenon are not yet elucidated. This study aimed to reveal the nature of the immune response in post-transplanted allergic patients and compare them to non-allergic transplanted as well as allergic and non-allergic control subjects, with focus on cytokine milieu. Post-liver transplant patients with and without allergic reactions as well as food-allergic but otherwise healthy and healthy non-allergic control patients were recruited. We reviewed patient records and routine laboratory tests and assayed subjects' PBMCs, studying cytokine secretion profile in response to different stimuli. Post-transplant patients with food allergy showed a unique cytokine profile in response to various stimuli, with extremely elevated IL-5, low IL-10 secretion, and somewhat higher IFN-γ. T regulatory cell number was not significantly different among the groups of patients and controls. Immune response of food-allergic post-liver transplant patients is identified by a unique cytokine profile when compared to allergic but otherwise healthy individuals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Allergic sensitization and filaggrin variants predispose to the comorbidity of eczema, asthma, and rhinitis: results from the Isle of Wight birth cohort

PubMed Central

Ziyab, Ali H.; Karmaus, Wilfried; Zhang, Hongmei; Holloway, John W.; Steck, Susan E.; Ewart, Susan; Arshad, Syed Hasan

2014-01-01

Background Allergic sensitization and filaggrin gene (FLG) variants are important risk factors for allergic disorders; however, knowledge on their individual and interactive effects on the coexistence of eczema, asthma, and rhinitis is lacking. Objective This study aimed at investigating the single and combined effects of allergic sensitization and FLG variants on the development of single and multiple allergic disorders. Methods The Isle of Wight Birth Cohort (n = 1,456) has been examined at 1, 2, 4, 10, and 18 years of age. Repeated measurements of eczema, asthma, rhinitis, and skin prick tests were available for all follow-ups. FLG variants were genotyped in 1,150 participants. Associations of allergic sensitization and FLG variants with single and multiple allergic disorders were tested in log-binomial regression analysis. Results The prevalence of eczema-, asthma-, and rhinitis-only ranged from 5.6% to 8.5%, 4.9% to 10.2%, and 2.5% to 20.4%, respectively, during the first 18 years of life. The coexistence of allergic disorders is common, with approximately 2% of the population reporting the comorbidity of “eczema, asthma, and rhinitis” during the study period. In repeated measurement analyses, allergic sensitization and FLG variants, when analyzed separately, were associated with having single and multiple allergic disorders. Of particular significance, their combined effect increased the risk of “eczema and asthma” (RR = 13.67, 95% CI: 7.35 – 25.42), “asthma and rhinitis” (RR = 7.46, 95% CI: 5.07 – 10.98), and “eczema, asthma, and rhinitis” (RR = 23.44, 95% CI: 12.27 – 44.78). Conclusions and Clinical Relevance The coexistence of allergic disorders is frequent and allergic sensitization and FLG variants jointly increased risk of allergic comorbidities, which may represent more severe and complex clinical phenotypes. The interactive effect and the elevated proportion of allergic comorbidities associated with allergic sensitization and FLG variants emphasize their joint importance in the pathogenesis of allergic disorders. PMID:24708301

Home and allergic characteristics of children with asthma in seven U.S. urban communities and design of an environmental intervention: the Inner-City Asthma Study.

PubMed Central

Crain, Ellen F; Walter, Michelle; O'Connor, George T; Mitchell, Herman; Gruchalla, Rebecca S; Kattan, Meyer; Malindzak, George S; Enright, Paul; Evans, Richard; Morgan, Wayne; Stout, James W

2002-01-01

Most published environmental remediation interventions have been directed at single allergens and have employed demanding strategies; few have been performed in the homes of inner-city children disproportionately burdened by asthma. Our objective was a) to describe the allergen sensitivities, environmental tobacco smoke (ETS) exposure, and home environmental characteristics of a national sample of inner-city children with moderate to severe asthma and b) to develop and implement a multifaceted, home-based comprehensive intervention to reduce home allergens and ETS, tailored to the specific sensitization and exposure profiles of those children. Allergen skin testing and a home evaluation were performed to determine the presence of ETS and factors known to be associated with increased indoor allergen levels. Based on published remediation techniques, a home environmental intervention, organized into modules, each addressing one of five specific allergen groups or ETS, was designed. Of 994 allergic children from seven U.S. urban communities, 937 successfully completed baseline interviews and home allergen surveys and were enrolled. More than 50% of children had positive skin tests to three or more allergen groups. Cockroaches were reported in 58% of homes, wall-to-wall carpeting in the child's bedroom in 55%, a smoker in 48%, mice or rats in 40%, and furry pets in 28%. More than 60% of enrolled families received four or more modules, and between 94% and 98% of all modules were completed. We conclude that most inner-city children with moderate to severe asthma are sensitized to multiple indoor allergens and that environmental factors known to be associated with asthma severity are commonly present in their homes. The intervention developed for the Inner-City Asthma Study employs accepted methods to address an array of allergens and ETS exposure while ensuring that the intervention is tailored to the specific sensitization profiles and home characteristics of these children. PMID:12204830

Allergic constitution theory of Chinese medicine and its assessment criterion and related studies.

PubMed

Wang, Ji; Wang, Ting; Li, Ying-shuai; Li, Ling-ru; Zheng, Yan-fei; Wang, Qi

2015-09-01

Constitution factor plays an important role in the occurrence, development, and transformation of diseases. The occurrence of allergic diseases is mainly caused by the disorganized physiological function and suitability regulation of patients, except for their exposure to outside allergens. Moreover, it represents susceptibility and hypersensitivity to allergens. The current study expresses the concept of allergic constitution from the perspective of Chinese medicine (CM) and presents the criterion of allergic constitution. In addition, the distribution of allergic constitution in population, its factors, and its relation to health-related quality of life (HRQOL) were investigated. The HRQOL scores of allergic constitution were found to be lower than those of the Pinghe constitution. After making a study on the gene expression profile of allergic constitution, the characteristics of up-regulated or down-regulated genes were found. Finally, CM drug was researched and developed to improve allergic constitution. Based on clinical trials and animal experiments, CM is found to have good regulatory effects on allergic constitution.

Recent developments in the role of reactive oxygen species in allergic asthma

PubMed Central

Qu, Jingjing; Li, Yuanyuan; Zhong, Wen

2017-01-01

Allergic asthma has a global prevalence, morbidity, and mortality. Many environmental factors, such as pollutants and allergens, are highly relevant to allergic asthma. The most important pathological symptom of allergic asthma is airway inflammation. Accordingly, the unique role of reactive oxygen species (ROS) had been identified as a main reason for this respiratory inflammation. Many studies have shown that inhalation of different allergens can promote ROS generation. Recent studies have demonstrated that several pro-inflammatory mediators are responsible for the development of allergic asthma. Among these mediators, endogenous or exogenous ROS are responsible for the airway inflammation of allergic asthma. Furthermore, several inflammatory cells induce ROS and allergic asthma development. Airway inflammation, airway hyper-responsiveness, tissue injury, and remodeling can be induced by excessive ROS production in animal models. Based on investigations of allergic asthma and ROS formation mechanisms, we have identified several novel anti-inflammatory therapeutic treatments. This review describes the recent data linking ROS to the pathogenesis of allergic asthma. PMID:28203435

Cytokine expression in the colostral cells of healthy and allergic mothers.

PubMed

Hrdý, Jiří; Novotná, Olga; Kocourková, Ingrid; Prokešová, Ludmila

2012-05-01

There is no doubt about the beneficial effect of breastfeeding on the newborn's immune system. It is not fully elucidated what the differences are between the colostrum/milk of healthy and allergic mothers and how beneficial breastfeeding by an allergic mother is. The gene expression of selected cytokines was tested in cells isolated from colostra of healthy and allergic mothers using quantitative real-time PCR. Allergic phenotype was evident in colostral cells of allergic mothers: gene expressions of IL-4, IL-13 and EGF were increased and those of IFN-gamma decreased in comparison with colostral cells of healthy mothers. The allergic phenotype of the colostral cells of allergic mothers supporting the bias to a Th2 type response was found. It remains a question if a small number of these cells could influence the immature newborn immune system.

Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response.

PubMed Central

Remirez, D; Ledón, N; González, R

2002-01-01

It has recently been reported that phycocyanin, a biliprotein found in the blue-green microalgae Spirulina, exerts anti-inflammatory effects in some animal models of inflammation. Taking into account these findings, we decided to elucidate whether phycocyanin might exert also inhibitory effects in the induced allergic inflammatory response and on histamine release from isolated rat mast cells. In in vivo experiments, phycocyanin (100, 200 and 300mg/kg post-orally (p.o.)) was administered 1 h before the challenge with 1 microg of ovalbumin (OA) in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase activity and ear edema were assessed. Phycocyanin significantly reduced both parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o.) also reduced the blue spot area induced by intradermal injections of histamine, and the histamine releaser compound 48/80 in rat skin. In concordance with the former results, phycocyanin also significantly reduced histamine release induced by compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of phycocyanin were dose dependent. Taken together, our results suggest that inhibition of allergic inflammatory response by phycocyanin is mediated, at least in part, by inhibition of histamine release from mast cells. PMID:12061428

Noninvasive Recognition and Biomarkers of Early Allergic Asthma in Cats Using Multivariate Statistical Analysis of NMR Spectra of Exhaled Breath Condensate

PubMed Central

Fulcher, Yan G.; Fotso, Martial; Chang, Chee-Hoon; Rindt, Hans; Reinero, Carol R.

2016-01-01

Asthma is prevalent in children and cats, and needs means of noninvasive diagnosis. We sought to distinguish noninvasively the differences in 53 cats before and soon after induction of allergic asthma, using NMR spectra of exhaled breath condensate (EBC). Statistical pattern recognition was improved considerably by preprocessing the spectra with probabilistic quotient normalization and glog transformation. Classification of the 106 preprocessed spectra by principal component analysis and partial least squares with discriminant analysis (PLS-DA) appears to be impaired by variances unrelated to eosinophilic asthma. By filtering out confounding variances, orthogonal signal correction (OSC) PLS-DA greatly improved the separation of the healthy and early asthmatic states, attaining 94% specificity and 94% sensitivity in predictions. OSC enhancement of multi-level PLS-DA boosted the specificity of the prediction to 100%. OSC-PLS-DA of the normalized spectra suggest the most promising biomarkers of allergic asthma in cats to include increased acetone, metabolite(s) with overlapped NMR peaks near 5.8 ppm, and a hydroxyphenyl-containing metabolite, as well as decreased phthalate. Acetone is elevated in the EBC of 74% of the cats with early asthma. The noninvasive detection of early experimental asthma, biomarkers in EBC, and metabolic perturbation invite further investigation of the diagnostic potential in humans. PMID:27764146

Environmental pollution and allergies.

PubMed

Takano, Hirohisa; Inoue, Ken-Ichiro

2017-07-01

Environmental changes are thought to be the main factor in the rapid increase and worsening of allergic diseases. While there have been significant changes in many environmental factors, including in environments such as residential, health and sanitation, food, and water/soil/atmospheric environments, the root of each of these changes is likely an increase in chemical substances. In fact, various environmental pollutants, such as air pollutants and chemical substances, have been shown to worsen various allergies in experimental studies. For example, diesel exhaust particles (DEPs), which are an agglomeration of particles and a wide array of chemical substances, aggravate asthma, primarily due to the principle organic chemical components of DEPs. In addition, environmental chemicals such as phthalate esters, which are commonly used as plasticizers in plastic products, also aggravate atopic dermatitis. It has also become evident that extremely small nanomaterials and Asian sand dust particles can enhance allergic inflammation. While the underlying mechanisms that cause such aggravation are becoming clearer at the cellular and molecular levels, methods to easily and quickly evaluate (screen) the ever-increasing amount of environmental pollutants for exacerbating effects on allergies are also under development. To eliminate and control allergic diseases, medical measures are necessary, but it is also essential to tackle this issue by ameliorating environmental changes.

Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

PubMed

Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

Allergic Asthma Induced in Rhesus Monkeys by House Dust Mite (Dermatophagoides farinae)

PubMed Central

Schelegle, Edward S.; Gershwin, Laurel J.; Miller, Lisa A.; Fanucchi, Michelle V.; Van Winkle, Laura S.; Gerriets, Joan P.; Walby, William F.; Omlor, Amanda M.; Buckpitt, Alan R.; Tarkington, Brian K.; Wong, Viviana J.; Joad, Jesse P.; Pinkerton, Kent B.; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles G.

2001-01-01

To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4+ lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA. PMID:11141508

Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation.

PubMed

Hosoki, Koa; Itazawa, Toshiko; Boldogh, Istvan; Sur, Sanjiv

2016-02-01

To discuss the presence and role of neutrophils in asthma and allergic diseases, and outline the importance of pollen and cat dander-induced innate neutrophil recruitment in induction of allergic sensitization and allergic inflammation. Uncontrolled asthma is associated with elevated numbers of neutrophils, and levels of neutrophil-attracting chemokine IL-8 and IL-17 in bronchoalveolar lavage fluids. These parameters negatively correlate with lung function. Pollen allergens and cat dander recruit neutrophils to the airways in a toll-like receptor 4, myeloid differentiation protein-2, and chemokine (C-X-C motif) receptor (CXCR) 2-dependent manner. Repeated recruitment of activated neutrophils by these allergens facilitates allergic sensitization and airway inflammation. Inhibition of neutrophil recruitment with CXCR2 inhibitor, disruption of toll-like receptor 4, or small interfering RNA against myeloid differentiation protein-2 also inhibits allergic inflammation. The molecular mechanisms by which innately recruited neutrophils contribute to shifting the airway inflammatory response induced by allergens from neutrophilic to an eosinophilic-allergic is an area of active research. Recent studies have revealed that neutrophil recruitment is important in the development of allergic sensitization and inflammation. Inhibition of neutrophils recruitment may be a strategy to control allergic inflammation.

Stressors of School-age Children With Allergic Diseases: A Qualitative Study.

PubMed

Iio, Misa; Hamaguchi, Mana; Nagata, Mayumi; Yoshida, Koichi

2018-05-08

Most studies of stress in children with chronic diseases have been geared toward parents and caregivers have not considered allergic diseases together. This study aimed to identify the stressors associated with allergic diseases in Japanese school-age children. Stressors associated with allergic diseases of 11 school-age children (seven boys and four girls; age range: 9-12 years) were investigated using semi-structured interviews. In the qualitative thematic analysis of stressors about allergic diseases, two themes: allergic disease-specific stressors and common stressors in chronic diseases, and 12 categories were identified. A thematic map was applied to four domains of stressor: physiological factors, psychological factors, social factors, and environmental factors. The results showed that school-age children with allergic diseases have a variety of stressors. Future studies should aim to develop an allergic disease-specific stress management program with school-age children. In children with allergic diseases, not only is stress management in daily life important, but also stress management for disease-specific matters to control the symptoms and maintain mental health. Stress management should be supported for school-age children with allergic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of rheumatoid arthritis with allergic diseases: A nationwide population-based cohort study.

PubMed

Lai, Ning-Sheng; Tsai, Tzung-Yi; Koo, Malcolm; Lu, Ming-Chi

2015-01-01

Low-grade inflammation conditions, e.g., type 2 diabetes, have been shown to be associated with an increased risk of rheumatoid arthritis (RA). However, the association between other chronic inflammatory conditions, e.g., asthma, allergic rhinitis, and atopic dermatitis, is still unclear. To investigate the risk of RA in patients with allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, by using a nationwide health claims database. The Taiwan National Health Insurance Research Database was used to assemble a cohort of 170,570 patients ages 20 years old and older diagnosed with allergic diseases, including asthma, allergic rhinitis, or atopic dermatitis. A comparison cohort of 170,238 patients was constructed from the same data base, with frequency matching for sex, 10-year age group, and year of insurance enrollment. Cox proportional hazards regression analyses were conducted to assess the association between the allergic diseases and incident RA. Asthma (adjusted hazard ratio [AHR] 1.67, [95% confidence interval {CI}], 1.32-2.62) and allergic rhinitis (AHR 1.62 [95% CI, 1.33-1.98]) were significantly associated with the incident RA. These associations remained significant even after excluding patients who had concurrent diagnoses of asthma and allergic rhinitis. Patients with more than one allergic disease had an increased risk of developing RA (AHR 1.98 [95% CI, 1.50-2.62]). Subgroup analysis further indicated that middle-aged and elderly female patients with more than one allergic disease exhibited a high risk of developing RA. Significant associations between common allergic diseases and incident RA was found in this population-based cohort study. Our findings provided support to the hypothesis that allergic diseases and RA might share a similar underlying etiologic pathway related to chronic inflammatory responses.

Preconceptional, prenatal and postnatal exposure to outdoor and indoor environmental factors on allergic diseases/symptoms in preschool children.

PubMed

Deng, Qihong; Lu, Chan; Ou, Cuiyun; Chen, Lv; Yuan, Hong

2016-06-01

Environmental factors have been found to be associated with allergic diseases, but it is unclear which environmental factor during which exposure window causes what kind of allergic diseases. We investigated association between exposure to some predominant outdoor and indoor environmental factors during preconceptional, prenatal, and postnatal periods and allergic diseases/symptoms in 2598 children in China. Children's lifetime incidence of allergic diseases and current prevalence of allergic symptoms and exposure to indoor new furniture/redecoration and mold/dampness was surveyed by a questionnaire. Exposure to outdoor air pollutants was estimated by the concentrations measured at air quality monitoring stations. Multiple logistic regression model was used to evaluate the associations between outdoor air pollutants and indoor environmental factors and allergic diseases (asthma, allergic rhinitis, and eczema) and symptoms (wheezing, night cough, and rhinitis-like). We found that preconceptional, prenatal, and postnatal exposure to outdoor industrial and traffic air pollutants were significantly associated with increase in the risk of childhood asthma, and also positively associated with allergic rhinitis and eczema. However, we cannot distinguish the effect of outdoor air pollutants and exposure windows because of their high correlations. New furniture was associated with eczema and allergic rhinitis during postnatal exposure, but redecoration associated with asthma and eczema during prenatal exposure. Indoor visible mold/damp stains was significant for eczema during prenatal exposure and asthma during postnatal exposure respectively, but window condensation was significant for all childhood allergic diseases during both prenatal and postnatal exposures. Allergic symptoms in children were found to be associated with exposure to indoor factors only. Associations between outdoor air pollutants and indoor environmental factors and childhood allergic diseases/symptoms were divergent and related to the timing of exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk factors associated with allergic and non-allergic asthma in adolescents.

PubMed

Janson, Christer; Kalm-Stephens, Pia; Foucard, Tony; Alving, Kjell; Nordvall, S Lennart

2007-07-01

Risk factors for asthma have been investigated in a large number of studies in adults and children, with little progress in the primary and secondary prevention of asthma. The aim of this investigation was to investigate risk factors associated with allergic and non-allergic asthma in adolescents. In this study, 959 schoolchildren (13-14 years old) answered a questionnaire and performed exhaled nitric oxide (NO) measurements. All children (n = 238) with reported asthma, asthma-related symptoms and/or increased NO levels were invited to a clinical follow-up which included a physician evaluation and skin-prick testing. Asthma was diagnosed in 96 adolescents, whereof half had allergic and half non-allergic asthma. Children with both allergic and non-allergic asthma had a significantly higher body mass index (BMI) (20.8 and 20.7 vs. 19.8 kg/m(2)) (p < 0.05) and a higher prevalence of parental asthma (30% and 32% vs. 16%) (p < 0.05). Early-life infection (otitis and croup) [adjusted odds ratio (OR) (95% confidence interval (CI)): 1.99 (1.02-3.88) and 2.80 (1.44-5.42), respectively], pets during the first year of life [2.17 (1.16-4.04)], window pane condensation [2.45 (1.11-5.40)] and unsatisfactory school cleaning [(2.50 (1.28-4.89)] was associated with non-allergic but not with allergic asthma. This study indicates the importance of distinguishing between subtypes of asthma when assessing the effect of different risk factors. While the risk of both allergic and non-allergic asthma increased with increasing BMI, associations between early-life and current environmental exposure were primarily found in relation to non-allergic asthma.

Genetic Variation along the Histamine Pathway in Children with Allergic versus Nonallergic Asthma

PubMed Central

Anvari, Sara; Vyhlidal, Carrie A.; Dai, Hongying

2015-01-01

Histamine is an important mediator in the pathogenesis of asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that differences exist among single-nucleotide polymorphisms (SNPs) in genes of the histamine pathway between children with allergic versus nonallergic asthma. Children (7–18 yr of age; n = 202) with asthma were classified as allergic or nonallergic based on allergy skin testing. Genotyping was performed to detect known SNPs (n = 10) among genes (HDC, HNMT, ABP1, HRH1, and HRH4) within the histamine pathway. Chi square tests and Cochran-Armitage Trend were used to identify associations between genetic variants and allergic or nonallergic asthma. Significance was determined by P < 0.05 and false-positive report probability. After correction for race differences in genotype were observed, HRH1-17 TT (6% allergic versus 0% nonallergic; P = 0.04), HNMT-464 TT (41% allergic versus 29% nonallergic; P = 0.04), and HNMT-1639 TT (30% allergic versus 20% nonallergic; P = 0.04) were overrepresented among children with allergic asthma. Genotype differences specifically among the African-American children were also observed: HRH1-17 TT (13% allergic versus 0% nonallergic; P = 0.04) and HNMT-1639 TT (23% allergic versus 3% nonallergic; P = 0.03) genotypes were overrepresented among African-American children with allergic asthma. Our study suggests that genetic variation within the histamine pathway may be associated with an allergic versus nonallergic asthma phenotype. Further studies are needed to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease. PMID:25909280

Disrupting the immune system by diesel pollution

EPA Science Inventory

For 25 years, clinical, animal and epidemiological studies have shown associations between diesel exhaust and allergic disease. Diesel particles have the potential to increase allergic symptoms, increase cellular inflammation enhance allergic antibodies and prime allergic sensit...

Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers

PubMed Central

Hoppin, Jane A.; Umbach, David M.; Long, Stuart; London, Stephanie J.; Henneberger, Paul K.; Blair, Aaron; Alavanja, Michael; Freeman, Laura E. Beane; Sandler, Dale P.

2016-01-01

Background: Growing evidence suggests that pesticide use may contribute to respiratory symptoms. Objective: We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. Methods: Using the 2005–2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent. Results: In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure–response models with up to five exposure categories, we saw evidence of an exposure–response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. Conclusions: These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects. Citation: Hoppin JA, Umbach DM, Long S, London SJ, Henneberger PK, Blair A, Alavanja M, Beane Freeman LE, Sandler DP. 2017. Pesticides are associated with allergic and non-allergic wheeze among male farmers. Environ Health Perspect 125:535–543; http://dx.doi.org/10.1289/EHP315 PMID:27384423

Nickel (Ni) allergic patients with complications to Ni containing joint replacement show preferential IL-17 type reactivity to Ni.

PubMed

Summer, Burkhard; Paul, Carina; Mazoochian, Farhad; Rau, Christoph; Thomsen, Marc; Banke, Ingo; Gollwitzer, Hans; Dietrich, Karin-Almut; Mayer-Wagner, Susanne; Ruzicka, Thomas; Thomas, Peter

2010-07-01

Some nickel (Ni) allergic patients develop complications following Ni-containing arthroplasty. In the peri-implant tissue of such patients, we had observed lymphocyte dominated inflammation together with IFN-gamma and IL-17 expression. To determine whether Ni stimulation of peripheral blood mononuclear cells (PBMCs) of such patients would lead to a different cytokine pattern as compared to Ni-allergic patients with symptom-free arthroplasty. Based on history and patch testing in 15 Ni-allergic patients (five without implant, five with symptom-free arthroplasty, five with complicated arthroplasty) and five non-allergic individuals, lymphocyte transformation test (LTT) was performed using PBMC. In parallel in vitro cytokine response to Ni was assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). All 15 Ni-allergic individuals showed enhanced LTT reactivity to Ni (mean SI = 8.42 +/- 1.8) compared to the non-allergic control group. Predominant IFN-gamma expression to Ni was found both in the five allergic patients without arthroplasty and also in the five allergic, symptom-free arthroplasty patients. In contrast, in the five Ni-allergic patients with arthroplasty-linked complications a predominant, significant IL-17 expression to Ni was seen but not in patients with symptom-free arthroplasty. The predominant IL-17 type response to Ni may characterize a subgroup of Ni-allergic patients prone to develop lymphocytic peri-implant hyper-reactivity.

Recent Patents and Emerging Therapeutics in the Treatment of Allergic Conjunctivitis

PubMed Central

Mishra, Gyan P.; Tamboli, Viral; Jwala, Jwala; Mitra, Ashim K.

2011-01-01

Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, non-steroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. PMID:21171952

Local and Systemic Effects of Unpolymerised Monomers

PubMed Central

Gosavi, Sulekha Siddharth; Gosavi, Siddharth Yuvraj; Alla, Rama Krishna

2010-01-01

Methyl methacrylate (MMA), a widely used monomer in dentistry and medicine has been reported to cause abnormalities or lesions in several organs. Experimental and clinical studies have documented that monomers may cause a wide range of adverse health effects such as irritation to skin, eyes, and mucous membranes, allergic dermatitis, stomatitis, asthma, neuropathy, disturbances of the central nervous system, liver toxicity, and fertility disturbances. PMID:22013462

Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

PubMed

Matheson, M C; Walters, E H; Simpson, J A; Wharton, C L; Ponsonby, A-L; Johns, D P; Jenkins, M A; Giles, G G; Hopper, J L; Abramson, M J; Dharmage, S C

2009-03-01

The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis suggest that family structure and infections have most impact on disease risk in early life. Further research should focus on early onset allergic rhinitis when exploring causal explanations for any sibling effect.

Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

PubMed

Mathers, A R; Carey, C D; Killeen, M E; Diaz-Perez, J A; Salvatore, S R; Schopfer, F J; Freeman, B A; Falo, L D

2017-04-01

Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO 2 -FAs), such as nitro oleic acid (OA-NO 2 ) and nitro linoleic acid (LNO 2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO 2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO 2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. We evaluated the effect of OA-NO 2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. We found that subcutaneous (SC) OA-NO 2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO 2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO 2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO 2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. Overall, these results support the development of OA-NO 2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Immunotherapeutic efficacy of liposome-encapsulated refined allergen vaccines against Dermatophagoides pteronyssinus allergy.

PubMed

Chaisri, Urai; Tungtrongchitr, Anchalee; Indrawattana, Nitaya; Meechan, Panisara; Phurttikul, Watchara; Tasaniyananda, Natt; Saelim, Nawannaporn; Chaicumpa, Wanpen; Sookrung, Nitat

2017-01-01

Allergen specific immunotherapy (AIT) can modulate the allergic response causing a long-term symptom subsidence/abolishment which leads to reduced drug use and prevention of new sensitization. AIT of house dust mite allergy (HDM) using the mite crude extract (CE) as the therapeutic agent is not only less effective than the AIT for many other allergens, but also frequently causes adverse effects during the treatment course. In this study, mouse model of Dermatophagoides pteronyssinus (Dp) allergy was invented for testing therapeutic efficacies of intranasally administered liposome (L) encapsulated vaccines made of single Dp major allergens (L-Der p 1, L-Der p 2), combined allergens (L-Der p 1 and Der p 2), and crude Dp extract (L-CE). The allergen sparing intranasal route was chosen as it is known that the effective cells induced at the nasal-associated lymphoid tissue can exert their activities at the lower respiratory tissue due to the common mucosal traffic. Liposome was chosen as the vaccine delivery vehicle and adjuvant as the micelles could reduce toxicity of the entrapped cargo. The Dp-CE allergic mice received eight doses of individual vaccines/placebo on alternate days. All vaccine formulations caused reduction of the Th2 response of the Dp allergic mice. However, only the vaccines made of single refined allergens induced expressions of immunosuppressive cytokines (TGF-β, IL-35 and/or IL-10) which are the imperative signatures of successful AIT. The data emphasize the superior therapeutic efficacy of single refined major allergen vaccines than the crude allergenic extract vaccine.

Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Ken-ichiro; Koike, Eiko; Yanagisawa, Rie

The development of nanotechnology has increased the risk of exposure to types of particles other than combustion-derived particles in the environment, namely, industrial nanomaterials. On the other hand, patients with bronchial asthma are sensitive to inhaled substances including particulate matters. This study examined the effects of pulmonary exposure to a type of nano-sized carbon nanotube (multi-walled nanotubes: MWCNT) on allergic airway inflammation in vivo and their cellular mechanisms in vitro. In vivo, ICR mice were divided into 4 experimental groups. Vehicle, MWCNT (50 {mu}g/animal), ovalbumin (OVA), and OVA + MWCNT were repeatedly administered intratracheally. Bronchoalveolar lavage (BAL) cellularity, lung histology,more » levels of cytokines related to allergic inflammation in lung homogenates/BAL fluids (BALFs), and serum immunoglobulin levels were studied. Also, we evaluated the impact of MWCNT (0.1-1 {mu}g/ml) on the phenotype and function of bone marrow-derived dendritic cells (DC) in vitro. MWCNT aggravated allergen-induced airway inflammation characterized by the infiltration of eosinophils, neutrophils, and mononuclear cells in the lung, and an increase in the number of goblet cells in the bronchial epithelium. MWCNT with allergen amplified lung protein levels of Th cytokines and chemokines compared with allergen alone. MWCNT exhibited adjuvant activity for allergen-specific IgG{sub 1} and IgE. MWCNT significantly increased allergen (OVA)-specific syngeneic T-cell proliferation, particularly at a lower concentration in vitro. Taken together, MWCNT can exacerbate murine allergic airway inflammation, at least partly, via the promotion of a Th-dominant milieu. In addition, the exacerbation may be partly through the inappropriate activation of antigen-presenting cells including DC.« less

Spontaneous food allergy in Was-/- mice occurs independent of FcεRI-mediated mast cell activation.

PubMed

Lexmond, W S; Goettel, J A; Sallis, B F; McCann, K; Rings, E H H M; Jensen-Jarolim, E; Nurko, S; Snapper, S B; Fiebiger, E

2017-12-01

Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was -/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was -/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was -/- Fcer1a -/- mice. Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was -/- model. Oral administration of ovalbumin (OVA) in Was -/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was -/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was -/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. Was -/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

PubMed

Polukort, Stephanie H; Rovatti, Jeffrey; Carlson, Logan; Thompson, Chelsea; Ser-Dolansky, Jennifer; Kinney, Shannon R M; Schneider, Sallie S; Mathias, Clinton B

2016-06-15

IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression. In contrast, the development of intestinal anaphylaxis, including diarrhea, mast cell activation, and Th2 cytokine production, was significantly attenuated in IL-10(-/-) mice compared with wild-type (WT) controls. IL-10 also directly promoted the expansion, survival, and activation of mast cells; increased FcεRI expression on mast cells; and enhanced the production of mast cell cytokines. IL-10(-/-) mast cells had reduced functional capacity, which could be restored by exogenous IL-10. Similarly, attenuated passive anaphylaxis in IL-10(-/-) mice could be restored by IL-10 administration. The adoptive transfer of WT mast cells restored allergic symptoms in IL-10(-/-) mice, suggesting that the attenuated phenotype observed in these animals is due to a deficiency in IL-10-responding mast cells. Lastly, transfer of WT CD4 T cells also restored allergic diarrhea and intestinal mast cell numbers in IL-10(-/-) mice, suggesting that the regulation of IL-10-mediated intestinal mast cell expansion is T cell dependent. Our observations demonstrate a critical role for IL-10 in driving mucosal mast cell expansion and activation, suggesting that, in its absence, mast cell function is impaired, leading to attenuated food allergy symptoms. Copyright © 2016 by The American Association of Immunologists, Inc.

Prevalence of allergic rhinitis among elementary and middle school students in Changsha city and its impact on quality of life.

PubMed

Song, Y; Wang, M; Xie, J; Li, W; Zhang, X; Wang, T; Tan, G

2015-11-01

To investigate the prevalence of allergic rhinitis among elementary and middle school students and examine its impact on their quality of life. Stratified sampling and cluster sampling surveys were performed among 10-17-year-old students in Changsha city from June 2011 to April 2012. In the stratified sampling survey, the self-reported allergic rhinitis rate was 42.5 per cent. Further examination demonstrated that the average prevalence of allergic rhinitis was 19.4 per cent. The cluster sampling survey demonstrated that 214 of 814 students appeared to be atopic (26.3 per cent). The prevalence of allergic rhinitis and asthma was 17.2 and 2.1 per cent, respectively. In total, 71 atopic individuals (8.7 per cent) were without any symptoms of allergic disease. Further analysis showed that allergic rhinitis influenced the students' sleep, emotions and memory (p < 0.001). The prevalence of allergic rhinitis was 15.8 -19.4 per cent, showing an increase with age. Allergic rhinitis affected students' sleep, emotions and memory.

Japanese Guideline for Allergic Rhinitis 2014.

PubMed

Okubo, Kimihiro; Kurono, Yuichi; Fujieda, Shigeharu; Ogino, Satoshi; Uchio, Eiichi; Odajima, Hiroshi; Takenaka, Hiroshi

2014-09-01

Like asthma and atopic dermatitis, allergic rhinitis is an allergic disease, but of the three, it is the only type I allergic disease. Allergic rhinitis includes pollinosis, which is intractable and reduces quality of life (QOL) when it becomes severe. A guideline is needed to understand allergic rhinitis and to use this knowledge to develop a treatment plan. In Japan, the first guideline was prepared after a symposium held by the Japanese Society of Allergology in 1993. The current 7th edition was published in 2013, and is widely used today. To incorporate evidence based medicine (EBM) introduced from abroad, the most recent collection of evidence/literature was supplemented to the Practical Guideline for the Management of Allergic Rhinitis in Japan 2013. The revised guideline includes assessment of diagnosis/treatment and prescriptions for children and pregnant women, for broad clinical applications. An evidence-based step-by-step strategy for treatment is also described. In addition, the QOL concept and cost benefit analyses are also addressed. Along with Allergic Rhinitis and its Impact of Asthma (ARIA), this guideline is widely used for various clinical purposes, such as measures for patients with sinusitis, childhood allergic rhinitis, oral allergy syndrome, and anaphylaxis and for pregnant women. A Q&A section regarding allergic rhinitis in Japan was added to the end of this guideline.

Innate Immune Responses to Engineered Nanomaterials During Allergic Airway Inflammation

NASA Astrophysics Data System (ADS)

Shipkowski, Kelly Anne

The field of nanotechnology is continually advancing, and increasing amounts of consumer goods are being produced using engineered nanomaterials (ENMs). The health risks of occupational and/or consumer exposure to ENMs are not completely understood, although significant research indicates that pulmonary exposure to nanomaterials induces toxic effects in the lungs of exposed animals. Multi-walled carbon nanotubes (MWCNTs) are a specific category of ENMs and consist of sheets of graphene rolled into cylinders that are multiple layers thick in order to strengthen their rigidity. MWCNTs have a fiber-like shape, similar to that of asbestos, which allows for a high aspect ratio and makes them difficult to clear from the lung. Studies with rodent models have demonstrated that pulmonary exposure to ENMs, in particular MWCNTs, results in acute lung inflammation and the subsequent development of chronic fibrosis, suggesting a potential human health risk to individuals involved in the manufacturing of products utilizing these nanomaterials. Induction of IL-1beta secretion via activation of the inflammasome is a prime mechanism of MWCNT-induced inflammation. The inflammasome is a multi-protein scaffold found in a variety of cell types that forms in response to a variety of immune signals, including particulates. Sensitization with allergens, such as house dust mite (HDM), increases levels of the T helper 2 (Th2) cytokines IL-4 and IL-13 in mice and in humans, and there is particular cause for concern in cases of MWCNT exposure in individuals with pre-existing allergic airway disease, such as asthma. MWCNT exposure exacerbates airway inflammation and fibrosis in animal models of pre-existing allergic asthma, suggesting that individuals suffering from asthma are more susceptible to the toxic pulmonary effects of MWCNT exposure. Asthma is an exceptionally prominent human disease, and therefore the goal of this research was to better understand how pre-existing allergic airway disease would modulate the innate immune response to MWCNTs. We hypothesized that Th2 cytokines and the allergic asthmatic microenvironment would alter MWCNT-induced inflammasome activation and IL- 1beta secretion both in vitro and in vivo. In vitro, THP-1 cells, a human monocytic cell line, were differentiated into macrophages and exposed to MWCNTs and or recombinant Th2 cytokines, specifically IL-4 and/or IL-13. Exposure of THP-1 cells to MWCNTs alone caused dose-dependent secretion of IL-1beta, while co-exposure to IL-4 and/or IL-13 suppressed MWCNT-induced IL-1beta. Further analysis determined that IL-4 and IL-13 were phosphorylating the protein signal transducer and activator of transcription 6 (STAT6) and subsequently inhibiting inflammasome activation and function through suppression of caspase-1, a cysteine protease responsible for cleavage of pro-IL-1beta into an active, secretable form. In vivo, wild-type C57BL6 mice were sensitized intranasally with HDM allergen and exposed to MWCNTs via oropharyngeal aspiration. Treatment with MWCNTs alone induced secretion of IL-1beta in the bronchoalveolar lavage fluid (BALF) one day post-exposure, while sensitization with HDM prior to MWCNT exposure suppressed MWCNT-induced IL-1beta. Immunohistochemical (IHC) analysis of lung sections from exposed animals showed that HDM sensitization inhibited MWCNT-induced pro-casapse-1 protein expression, responsible for inflammasome activation, in the airway epithelium and macrophages. MWCNT exposure combined with HDM sensitization increased inflammatory cell infiltration and subsequent acute lung inflammation and chronic fibrosis. Analysis of the systemic effects of MWCNT exposure during allergic airway sensitization showed that MWCNTs and/or HDM allergen upregulated STAT3 mRNA expression in the lungs, liver, and spleen of exposed animals, and at the same induced mixed T helper (Th) responses in the different tissues. Collectively, these data suggest that the allergic microenvironment induced during asthma can modulate the innate inflammatory response to MWCNTs through inhibition of caspase-1 and inflammasome activation in the lung and through alteration of the transcription factors involved in the T helper immune responses systemically.

DOSE-DEPENDENT ALLERGIC ASTHMA RESPONSES TO PENICILLIUM CHRYSOGENUM

EPA Science Inventory

ABSTRACT
Indoor mold has been associated with development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and its viable conidia can induce allergic responses in a mouse model of allergic penicilliosis. The hypothesis o...

Dietary primary prevention of allergic diseases in children: the Philippine guidelines

PubMed Central

Recto, Marysia Stella T.; Genuino, Maria Lourdes G.; Casis-Hao, Roxanne J.; Tamondong-Lachica, Diana R.; Sales, Maria Imelda V.; Tan, Marilou G.; Mondonedo, Karen S.; Dionisio-Capulong, Regina C.

2017-01-01

Allergic diseases, such as asthma, allergic rhinitis, eczema, and food allergy, are preventable diseases. Primary prevention strategies of allergic diseases have been in scrutiny. Effective prevention strategies maybe started prenatally, postnatally, during infancy, and even during childhood. These guidelines have been prepared by the Philippine Society of Allergy, Asthma and Immunology and the Philippine Society for Pediatric Gastroenterology, Hepatology and Nutrition. They aim to provide evidence-based recommendations for the dietary primary prevention of allergic diseases in children. The primary audience of these guidelines is all healthcare practitioners who manage patients with potential allergic conditions. These guidelines are based on an exhaustive review of evidences, mostly systematic reviews, randomized controlled trials, and cohort studies. However, there are still many gaps in the evidence of dietary primary prevention of allergic diseases. PMID:28487842

Obese and Allergic Related Asthma Phenotypes Among Children Across the United States.

PubMed

Ross, Mindy K; Romero, Tahmineh; Sim, Myung S; Szilagyi, Peter G

2018-04-19

Pediatric asthma is heterogeneous with phenotypes that reflect differing underlying inflammation and pathophysiology. Little is known about the national prevalence of certain obesity and allergy related asthma phenotypes or associated characteristics. We therefore assessed the national prevalence, risk factors, and parent-reported severity of four asthma phenotypes: not-allergic-not-obese, allergic-not-obese, obese-not-allergic, and allergic-and-obese. We analyzed data from the 2007-2008 National Survey of Children's Health (NSCH) of 10-17 year-olds with parent-reported asthma. We described sociodemographic and health risk factors of each phenotype and then applied logistic and ordinal regression models to identify associated risk factors and level of severity of the phenotypes. Among 4,427 children with asthma in this NSCH cohort, the association between race and phenotype is statistically significant (p<0.0001); white children with asthma were most likely to have allergic-not-obese asthma while black and Hispanic children with asthma were most likely to have the obese-non-allergic phenotype (p<0.001). ADD/ADHD was more likely to be present in allergic-not-obese children (OR 1.50, CI 1.14-1.98, p = 0.004). The phenotype with the highest risk for more severe compared to mild asthma was the obese-and-allergic asthma phenotype (OR 3.34, CI 2.23-5.01, p<0.001). Allergic-not-obese asthma comprised half of our studied asthma phenotypes, while obesity-related asthma (with or without allergic components) comprised one-fifth of asthma phenotypes in this cohort representative of the U.S. Children with both obese and allergic asthma are most likely to have severe asthma. Future management of childhood asthma might consider more tailoring of treatment and management plans based upon different childhood asthma phenotypes.

Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers.

PubMed

Hoppin, Jane A; Umbach, David M; Long, Stuart; London, Stephanie J; Henneberger, Paul K; Blair, Aaron; Alavanja, Michael; Freeman, Laura E Beane; Sandler, Dale P

2017-04-01

Growing evidence suggests that pesticide use may contribute to respiratory symptoms. We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. Using the 2005-2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever ( n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever ( n = 3,939, 18%); men without wheeze were the referent. In models evaluating current use of specific pesticides, 19 pesticides were significantly associated ( p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure-response models with up to five exposure categories, we saw evidence of an exposure-response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects.

Age-Related Changes in Immunological Factors and Their Relevance in Allergic Disease Development During Childhood.

PubMed

Chang, Woo Sung; Kim, Eun Jin; Lim, Yeon Mi; Yoon, Dankyu; Son, Jo Young; Park, Jung Won; Hong, Soo Jong; Cho, Sang Heon; Lee, Joo Shil

2016-07-01

Allergic diseases are triggered by Th2-mediated immune reactions to allergens and orchestrated by various immunological factors, including immune cells and cytokines. Although many reports have suggested that childhood is the critical period in the onset of allergic diseases and aging leads to alter the susceptibility of an individual to allergic diseases, age-related changes in various immunological factors in healthy individuals as well as their difference between healthy and allergic children have not yet been established. We investigated the ratio of Th1/Th2 cells and the levels of 22 allergy-related cytokines across all age groups in individuals who were classified as clinically non-atopic and healthy. We also examined their differences between healthy and allergic children to evaluate immunological changes induced by the development of allergic diseases during childhood. The Th1/Th2 ratio rose gradually during the growth period including childhood, reaching peak values in the twenties-thirties age group. Th1/Th2 ratios were significantly lower in allergic children than in healthy controls, whereas 14 of 22 cytokines were significantly higher in allergic children than in healthy controls. On the other hand, there were no differences in Th1/Th2 ratios and cytokines between healthy and allergic adolescents. In this study, age-related changes in Th1/Th2 ratios were found in normal controls across all age groups, and decreases in Th1/Th2 ratio were observed with increasing of 14 cytokines in allergic children. The results of this study may be helpful as reference values for both monitoring immunological changes according to aging in healthy individuals and distinguishing between normal and allergic subjects in terms of immune cells and soluble factors.

Local Effect of Neurotrophin-3 in Neuronal Inflammation of Allergic Rhinitis: Preliminary Report.

PubMed

İsmi, Onur; Özcan, Cengiz; Karabacak, Tuba; Polat, Gürbüz; Vayisoğlu, Yusuf; Güçlütürk, Taylan; Görür, Kemal

2015-10-01

Allergic rhinitis is a common inflammatory nasal mucosal disease characterized by sneezing, watery nasal discharge, nasal obstruction and itching. Although allergen-specific antibodies play a main role in the allergic airway inflammation, neuronal inflammation may also contribute to the symptoms of allergic rhinitis. Neuronal inflammation is primarily caused by the stimulation of sensory nerve endings with histamine. It has been shown that neurotrophins may also have a role in allergic reactions and neuronal inflammation. Nerve growth factor, neurotrophin 3 (NT-3), neurotrophin 4/5 and brain-derived neurotrophic factor are members of the neurotrophin family. Although nerve growth factor and brain-derived neurotrophic factor are well studied in allergic rhinitis patients, the exact role of Neurotrophin-3 is not known. To investigate the possible roles of neurotrophin-3 in allergic rhinitis patients. Case-control study. Neurotrophin-3 levels were studied in the inferior turbinate and serum samples of 20 allergic rhinitis and 13 control patients. Neurotrophin-3 staining of nasal tissues was evaluated by immunohistochemistry and ELISA was used for the determination of serum Neurotrophin-3 levels. Neurotrophin-3 staining scores were statistically higher in the study group than in the control patients (p=0.001). Regarding serum Neurotrophin-3 levels, no statistically significant difference could be determined between allergic rhinitis and control patients (p=0.156). When comparing the serum NT-3 levels with tissue staining scores, there were no statistically significant differences in the allergic rhinitis and control groups (p=0.254 for allergic rhinitis and p=0.624 for control groups). We suggest that Neurotrophin-3 might affect the nasal mucosa locally without being released into the systemic circulation in allergic rhinitis patients.

TGF-Beta Gene Polymorphisms in Food Allergic versus Non-Food Allergic Eosinophilic Esophagitis

DTIC Science & Technology

2014-12-01

past reports, the majority of our EE subjects are male, Caucasian, and have another atopic disorder (asthma, allergy, eczema and/or food allergy...or skin prick testing positive Table 2: Co-existent Allergic Characteristics of Pediatric EoE Population Asthma (%) Allergic Rhinitis (%) Eczema ...Consistent with high rates of atopy in the EoE population, 36% had asthma, 53% had allergic rhinitis, 43% had eczema , and 42% had a an immediate

Recombinant allergens

PubMed Central

Jutel, Marek; Solarewicz-Madejek, Katarzyna; Smolinska, Sylwia

2012-01-01

Allergen specific immunotherapy (SIT) is the only known causative treatment of allergic diseases. Recombinant allergen-based vaccination strategies arose from a strong need to both to improve safety and enhance efficacy of SIT. In addition, new vaccines can be effective in allergies including food allergy or atopic dermatitis, which poorly respond to the current treatment with allergen extracts. A number of successful clinical studies with both wild-type and hypoallergenic derivatives of recombinant allergens vaccines have been reported for the last decade. They showed high efficacy and safety profile as well as very strong modulation of T and B cell responses to specific allergens. PMID:23095874

Effect of orally administered Lactobacillus brevis HY7401 in a food allergy mouse model.

PubMed

Lee, Jeongmin; Bang, Jieun; Woo, Hee-Jong

2013-11-28

We had found that orally administered Lactobacillus species were effective immune modulators in ovalbumin (OVA)-sensitized mice. To validate these findings, we investigated the effects of orally administered Lactobacillus brevis HY7401 in OVA-T cell receptor transgenic mice. This strain showed a tendency to induce Th1 cytokines and inhibit Th2 cytokines. All assayed isotypes of OVA-specific antibody were effectively reduced. Systemic anaphylaxis was also relatively reduced with the probiotic administration. These results reveal that L. brevis HY7401 might be useful to promote anti-allergic processes through oral administration.

An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and patents.

PubMed

Porchezhian, E; Dobriyal, R M

2003-01-01

Chemistry and pharmacology of Gymnema sylvestre is reviewed relying on research papers and patent literature. Extracts of this plant are widely used in Australian, Japananese, Vietnamese and Indian folk medicine. Gymnema preparations have a profound action on the modulation of taste, particularly suppressing sweet taste sensations. It is used in the treatment of diabetes mellitus and in food additives against obesity and caries. Anti-allergic, antiviral, lipid lowering and other effects are also reported. From a technological point of view, muchefforts have been made to mask the biter taste of Gymnema preparations.

Physical Activity, Sedentary Habits, Sleep, and Obesity are Associated with Asthma, Allergic Rhinitis, and Atopic Dermatitis in Korean Adolescents.

PubMed

Lim, Man Sup; Lee, Chang Hee; Sim, Songyong; Hong, Sung Kwang; Choi, Hyo Geun

2017-09-01

Since pathophysiologic evidence has been raised to suggest that obesity could facilitate an allergic reaction, obesity has been known as an independent risk factor for allergic disease such as asthma. However, the relationship between sedentary behavior and lifestyle which could lead to obesity, and those allergic diseases remains unclear. We analyzed the relations between physical activity, including sitting time for study, sitting time for leisure and sleep time, and obesity, asthma, allergic rhinitis, and atopic dermatitis using the Korea Youth Risk Behavior Web-based Survey, which was conducted in 2013. Total 53769 adolescent participants (12 through 18 years old) were analyzed using simple and multiple logistic regression analyses with complex sampling. Longer sitting time for study and short sitting time for leisure were associated with allergic rhinitis. High physical activity and short sleep time were associated with asthma, allergic rhinitis, and atopic dermatitis. Underweight was negatively associated with atopic dermatitis, whereas overweight was positively correlated with allergic rhinitis and atopic dermatitis. High physical activity, and short sleep time were associated with asthma, allergic rhinitis, and atopic dermatitis. © Copyright: Yonsei University College of Medicine 2017

DC type 2 polarization depends on both the allergic status of the individual and protease activity of Per a 10.

PubMed

Goel, Chhavi; Gaur, S N; Bhati, Gaurav; Arora, Naveen

2015-10-01

Cockroach proteases are important risk factors for asthma development in predisposed individuals. In the present study, effect of allergic status of patients on DCs polarization in response to protease allergen Per a 10 was investigated. Cockroach-allergic, other-allergic patients and healthy individuals were selected following the guidelines of ATS/ARIA. Monocyte-derived dendritic cells (DCs) were generated from the selected individuals and stimulated with Per a 10. Flow cytometric analysis showed a significantly high expression of CD80 and CD86 on DCs from cockroach-allergic patients after Per a 10 stimulation as compared to healthy individuals or other-allergic patients (P<0.05). Per a 10 induced comparable level of CD83 expression on DCs from all the 3 groups, showing it was irrespective of the allergic status. CD40 expression was significantly low (P<0.05) on the DCs from cockroach-allergic patients as compared to healthy individuals or other-allergic patients. Further, proteolytically active Per a 10 induced lower CD40 expression on DCs than the heat-inactivated Per a 10 (P<0.05) indicating role of protease activity in the generation of an immune response. The sCD40 level in active Per a 10 stimulated DC cultures was significantly higher than in heat-inactivated Per a 10 (P<0.05). There was two-fold decrease (P<0.05) in IL-12 production by active Per a 10-stimulated DCs than heat-inactivated Per a 10-stimulated DCs. Per a 10-stimulated DCs from cockroach-allergic patients secreted high levels of IL-5, IL-6, TNF-α than that from healthy individuals or other-allergic patients (P<0.05). Furthermore, Per a 10-stimulated DCs from cockroach-allergic patients induced increased secretions of IL-4, IL-5, IL-6, TNF-α and low IL-12 by T cells as compared to those from other groups (P<0.05). Thus, in presence of Per a 10 allergen, polarization of DCs shifts toward type 2 in cockroach-allergic patients but not in the healthy individuals or other-allergic patients. In conclusion, both allergic status of the individual and protease activity of Per a 10 are important parameters that participate in DCs polarization. Copyright © 2015 Elsevier GmbH. All rights reserved.

DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BALB/MICE

EPA Science Inventory

Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

Parasitic Nematode-Induced CD4+Foxp3+T Cells Can Ameliorate Allergic Airway Inflammation

PubMed Central

Kang, Shin Ae; Park, Mi-Kyung; Cho, Min Kyoung; Park, Sang Kyun; Jang, Min Seong; Yang, Bo-Gie; Jang, Myoung Ho; Kim, Dong-Hee; Yu, Hak Sun

2014-01-01

Background The recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system. Methodology/Principal Findings We compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells. Conclusion/Significance T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases. PMID:25522145

Associations between maternal antioxidant intakes in pregnancy and infant allergic outcomes.

PubMed

West, Christina E; Dunstan, Janet; McCarthy, Suzi; Metcalfe, Jessica; D'Vaz, Nina; Meldrum, Suzanne; Oddy, Wendy H; Tulic, Meri K; Prescott, Susan L

2012-11-14

Antioxidant intakes in pregnancy may influence fetal immune programming and the risk of allergic disease. We investigated associations between maternal intakes of β-carotene, vitamin C, vitamin E, copper and zinc, and infant allergic outcomes. Antioxidant intakes of pregnant women (n = 420) assessed prospectively by a food frequency questionnaire, were examined in relation to allergic outcomes at 1 year of age (n = 300). The main relationships with allergic outcomes were seen with dietary vitamin C and copper. Specifically, higher maternal dietary vitamin C intake was associated with a reduced risk of any diagnosed infant allergic disease and wheeze. After adjustment for potential confounders the relationship with wheeze remained statistically significant. There was also an inverse linear relationship between vitamin C and food allergy. Higher dietary copper intake was associated with reduced risk of eczema, wheeze and any allergic disease. The relationship with wheeze and any allergic disease remained statistically significant in multivariate analysis, and there was also an inverse linear relationship between copper and food allergy. However, these relationships were only seen for nutrients present in food. There were no relationships between β-carotene, vitamin E or zinc and any allergic outcomes. In summary, this study suggests that maternal diet of fresh foods rich in vitamin C is associated with reduced risk of infant wheeze, and that copper intake is associated with reduced risk of several allergic outcomes.

An algorithm recommendation for the pharmacological management of allergic rhinitis in the UK: a consensus statement from an expert panel.

PubMed

Lipworth, Brian; Newton, Jon; Ram, Bhaskar; Small, Iain; Schwarze, Jürgen

2017-01-23

Allergic rhinitis is a frequent presenting problem in primary care in the UK, and has increased in prevalence over the last 30 years. When symptomatic, patients report significant reduction in their quality of life and impairment in school and work performance. Achieving adequate symptom control is pivotal to successful allergic rhinitis management, and relies mostly on pharmacotherapy. While it is recognised that most mild-moderate allergic rhinitis symptoms can be managed successfully in primary care, important gaps in general practitioner training in relation to allergic rhinitis have been identified. With the availability of new effective combination therapies, such as the novel intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (Dymista®; Meda), the majority of allergic rhinitis symptoms can be treated in the primary care setting. The primary objective of this consensus statement is to improve diagnosis and treatment of allergic rhinitis in primary care, and offer guidance on appropriate referral of difficult-to-treat patients into secondary care. The guidance provided herein outlines a sequential treatment pathway for allergic rhinitis in primary care that incorporates a considered approach to improve the management of allergic rhinitis symptoms and improve compliance and patient satisfaction with therapy. Adherence with this care pathway has the potential to limit the cost of providing effective allergic rhinitis management in the UK by avoiding unnecessary treatments and investigations, and avoiding the need for costly referrals to secondary care in the majority of allergic rhinitis cases. The fundamentals presented in this consensus article should apply in most health-care settings.

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model

PubMed Central

2010-01-01

Background The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol. Objectives This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses. Methods Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 μg of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 μg of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE. Results Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 μg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses. Conclusions The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE. PMID:20433763

DOSE-DEPENDENT ALLERGIC RESPONSES TO AN EXTRACT OF PENICILLIUM CHRYSOGENUM IN BAL/C MICE

EPA Science Inventory

Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of ...

Peroxisome proliferator-activated receptor δ agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis

PubMed Central

Kanakasabai, Saravanan; Chearwae, Wanida; Walline, Crystal C; Iams, Wade; Adams, Suzanne M; Bright, John J

2010-01-01

Multiple sclerosis (MS) is a neurological disorder that affects more than a million people world-wide. The aetiology of MS is not known and there is no medical treatment available that can cure MS. Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune disease model of MS. The pathogenesis of EAE/MS is a complex process involving activation of immune cells, secretion of inflammatory cytokines and destruction of myelin sheath in the central nervous system (CNS). Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptor transcription factors that regulate cell growth, differentiation and homeostasis. PPAR agonists have been used in the treatment of obesity, diabetes, cancer and inflammation. We and others have shown that PPARγ, α and δ agonists inhibit CNS inflammation and demyelination in the EAE model of MS. In this study we show that the PPARδ agonists GW501516 and L165041 ameliorate MOGp35-55-induced EAE in C57BL/6 mice by blocking interferon (IFN)-γ and interleukin (IL)-17 production by T helper type 1 (Th1) and Th17 cells. The inhibition of EAE by PPARδ agonists was also associated with a decrease in IL-12 and IL-23 and an increase in IL-4 and IL-10 expression in the CNS and lymphoid organs. These findings indicate that PPARδ agonists modulate Th1 and Th17 responses in EAE and suggest their use in the treatment of MS and other autoimmune diseases. PMID:20406305

Upregulation of Mas-related G Protein coupled receptor X2 in asthmatic lung mast cells and its activation by the novel neuropeptide hemokinin-1.

PubMed

Manorak, Wichayapha; Idahosa, Chizobam; Gupta, Kshitij; Roy, Saptarshi; Panettieri, Reynold; Ali, Hydar

2018-01-03

Hemokinin-1 (HK-1) is a novel neuropeptide produced by human bronchial cells and macrophages and causes contraction of human bronchi ex vivo. It is also generated by antigen/IgE-activated murine mast cells (MCs) and contributes to experimental chronic allergic airway inflammation via the activation of the neurokinin receptor-1 (NK-1R) expressed on murine MCs. We found elevated MC numbers in the lungs of individuals who died from asthma (asthma) when compared to lungs of individuals who died from other causes (non-asthma). Mas-related G Protein coupled receptor X2 (MRGPRX2) is a novel G-protein coupled receptor (GPCR) that is expressed predominantly on human MCs. We detected low level of MRGPRX2 in non-asthma lung MCs but its expression was significantly upregulated in asthma lung MCs. HK-1 caused degranulation in a human MC line (LAD2) and RBL-2H3 cells stably expressing MRGPRX2 and this response was resistant to inhibition by an NK-1R antagonist. However, knockdown of MRGPRX2 in LAD2 cells resulted in substantial inhibition of HK-1-induced degranulation. These findings suggest that while HK-1 contributes to the development of experimental asthma in mice via NK-1R on murine MCs the effect of this neuropeptide on human bronchoconstriction likely reflects the activation of MRGPRX2 on lung MCs. Thus, development of selective MRGPRX2 antagonists could serve as novel target for the modulation of asthma.

Epigenomics and allergic disease.

PubMed

Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

2013-12-01

Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.

Helicobacter pylori infection and atopic diseases: Is there a relationship? A systematic review and meta-analysis

PubMed Central

Lionetti, Elena; Leonardi, Salvatore; Lanzafame, Angela; Garozzo, Maria Teresa; Filippelli, Martina; Tomarchio, Stefania; Ferrara, Viviana; Salpietro, Carmelo; Pulvirenti, Alfredo; Francavilla, Ruggiero; Catassi, Carlo

2014-01-01

AIM: To review and conduct a meta-analysis of the existing literature on the relationship between Helicobacter pylori (H. pylori), atopy and allergic diseases. METHODS: Studies published in English assessing the prevalence of atopy and/or allergic diseases in patients with H. pylori infection and the prevalence of H. pylori infection in patients with atopy and/or allergic diseases were identified through a MEDLINE search (1950-2014). Random-effect model was used for the meta-analysis. RESULTS: Pooled results of case-control studies showed a significant inverse association of H. pylori infection with atopy/allergic disease or with exclusively atopy, but not with allergic disease, whereas pooled results of cross-sectional studies showed only a significant association between allergic disease and H. pylori infection. CONCLUSION: There is some evidence of an inverse association between atopy/allergic diseases and H. pylori infection, although further studied are needed. PMID:25516679

Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.

PubMed

Coutinho, Agnes E; Brown, Jeremy K; Yang, Fu; Brownstein, David G; Gray, Mohini; Seckl, Jonathan R; Savill, John S; Chapman, Karen E

2013-01-01

Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses.

The role of leukotrienes in airway inflammation.

PubMed

Ogawa, Yoshiko; Calhoun, William J

2006-10-01

Cysteinyl leukotrienes (cysLTs) are a class of closely structurally related lipid molecules, originally described as slow-reacting substance of anaphylaxis, with a myriad of biologic functions. These activities include producing smooth muscle contraction and mucus secretion, recruiting allergic inflammatory cells, modulating cytokine production, influencing neural transmission, and altering structural changes in the airway. Administration of cysLTs to animals and human subjects reproduces many features of allergic inflammation and asthma. Leukotriene (LT) blockers have independent efficacy in asthma and improve pulmonary function when added to inhaled steroids. Conversely, blockade of this pathway both in animals and in human subjects results in important reductions in inflammation and its consequences and might reduce structural changes of remodeling. These data collectively make a compelling case for an important role of cysLTs in airway inflammation and asthma. However, the magnitude of effect of anti-LTs is smaller than that of corticosteroids, and there is more variability in benefit of LT blockade than is seen with inhaled steroids. In addition, adding anti-LTs to inhaled steroids in asthmatic patients does not appear to produce added anti-inflammatory benefit. Genetic polymorphisms and environmental factors, such as tobacco smoke exposure, might underlie some of the heterogeneity of response to LT blockers.

RELATIVE POTENCY OF MOLD AND HOUSE DUST MITE EXTRACTS IN INDUCING ALLERGIC RESPONSES IN BALB/C MICE

EPA Science Inventory

Rationale: Mold has been associated with the exacerbation of allergic asthma. However, its role in induction of allergic asthma is not clear. Using a previously developed mouse model for allergic asthma, we compared potencies of two fungal extracts (Metarhizium anisop...