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      The influence of atopy and asthma on immune responses in inner‐city adults

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          Abstract

          Asthma in the inner‐city population is usually atopic in nature, and is associated with significant morbidity and mortality. However, the underlying immune abnormalities that underlie asthma in urban adults have not been well defined. We investigated the influence of atopy and asthma on cytokine responses of inner‐city adult women to define immune abnormalities associated with asthma and atopy. Blood samples were collected from 509 of 606 inner‐city women enrolled in the Urban Environment and Childhood Asthma (URECA) study. We tested for associations between atopy and asthma status and cytokine responses in peripheral blood mononuclear cells incubated ex vivo with a panel of innate and adaptive immune stimulants. Atopic subjects had heightened Th2 cytokine responses (IL‐4, IL‐5, IL‐13) to cockroach and dust mite antigens, tetanus toxoid, and phytohemagglutinin ( P < 0.05 for all). Differences in cytokine responses were greatest in response to stimulation with cockroach and dust mite. In a multivariate analysis, atopy was broadly related to increased Th2‐like responses to all antigens and PHA, while asthma was only weakly related to mitogen‐induced IL‐4 and IL‐5 responses. There were few asthma or allergy‐related differences in responses to innate stimuli, including IFN‐α and IFN‐γ responses. In this inner‐city adult female population, atopy is associated with enhanced Th2 responses to allergens and other stimuli, and there was little or no additional signal attributable to asthma. In particular, these data indicate that altered systemic interferon and innate immune responses are not associated with allergies and/or asthma in inner‐city women.

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          Most cited references30

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          Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus

          Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
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            Role of deficient type III interferon-lambda production in asthma exacerbations.

            Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.
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              Role of viral respiratory infections in asthma and asthma exacerbations

              Summary Viral respiratory tract infections are common and usually selflimited illnesses. For patients at risk of asthma, or with existing asthma, viral respiratory tract infections can have a profound effect on the expression of disease or loss of control. New evidence has shown that wheezing episodes early in life due to human rhinoviruses are a major risk factor for the later diagnosis of asthma at age 6 years. For those with existing asthma, exacerbations are a major cause of morbidity, can need acute care, and can, albeit rarely, result in death. Viral respiratory tract infections, predominantly those caused by human rhinoviruses, are associated with asthma exacerbations. There is also evidence that deficiencies in antiviral activity and the integrity of the airway epithelial barrier could make individuals with asthma more likely to have severe viral respiratory infections of the lower airway, and thus increase the risk of exacerbation. In view of the effect of respiratory viruses on many aspects of asthma, efforts to understand the mechanisms and risk factors by which these airway infections cause changes in airway pathophysiology are a first step towards improved treatment.
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                Author and article information

                Journal
                Immun Inflamm Dis
                Immun Inflamm Dis
                10.1002/(ISSN)2050-4527
                IID3
                Immunity, Inflammation and Disease
                John Wiley and Sons Inc. (Hoboken )
                2050-4527
                26 February 2016
                March 2016
                : 4
                : 1 ( doiID: 10.1002/iid3.2016.4.issue-1 )
                : 80-90
                Affiliations
                [ 1 ] School of Medicine and Public HealthUniversity of Wisconsin Madison Wisconsin
                [ 2 ] Division of Federal SystemsRho Inc. Chapel Hill North Carolina
                [ 3 ] Department of Obstetrics and GynecologyJohns Hopkins University School of Medicine Baltimore Maryland
                [ 4 ] Department of Pulmonary MedicineBoston University School of Medicine Boston Massachusetts
                [ 5 ] Center for Immunology and Inflammatory Diseases and the Food Allergy CenterMassachusetts General Hospital and Harvard Medical School Boston Massachusetts
                [ 6 ] Division of Allergy and Pulmonary Medicine, Department of PediatricsWashington University School of Medicine and St. Louis Children's Hospital St. Louis Missouri
                Author notes
                [*] [* ] Correspondence

                Sujani Kakumanu, MD, Clinical Assistant Professor, School of Medicine and Public Health, University of Wisconsin, Middleton Veterans Memorial Hospital, 600 Highland Avenue CSC9988, Madison, WI 53705. Tel: +1 608 265 2206; Fax: 1 608 265 2207; E‐mail: ssk@ 123456medicine.wisc.edu

                Article
                IID396
                10.1002/iid3.96
                4768071
                27042305
                337bd7aa-5258-413e-9e8e-617db69ff4ff
                © 2016 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2015
                : 01 December 2015
                : 05 December 2015
                Page count
                Pages: 11
                Categories
                Original Research
                Original Research
                Custom metadata
                2.0
                iid396
                March 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:26.02.2016

                adults,atopy,asthma,cytokines,immune responses,immunology,inner‐city,maternal

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