Open AccessJournal Article
Interleukin-13: Central mediator of allergic asthma
Marsha Wills-Karp,Jackie Luyimbazi,Xueying Xu,Brian Schofield,Tamlyn Neben,Christopher L. Karp,Debra D. Donaldson +6 more
TLDR
In this article, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.Abstract:
The worldwide incidence, morbidity, and mortality of allergic asthma are increasing. The pathophysiological features of allergic asthma are thought to result from the aberrant expansion of CD4 + T cells producing the type 2 cytokines interleukin-4 (IL-4) and IL-5, although a necessary role for these cytokines in allergic asthma has not been demonstrable. The type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma. IL-13 induces the pathophysiological features of asthma in a manner that is independent of immunoglobulin E and eosinophils. Thus, IL-13 is critical to allergen-induced asthma but operates through mechanisms other than those that are classically implicated in allergic responses.read more
Citations
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Journal ArticleDOI
The Pathophysiology of Asthma
Lee A. Maddox,David A. Schwartz +1 more
TL;DR: The important influence of genetic and environmental factors on the emergence of the asthmatic phenotype is discussed, the significance of Th-1 and Th-2 lymphocyte-mediated immunity are discussed, and the inflammatory processes leading to chronic airway inflammation are detailed.
Journal ArticleDOI
Enhanced innate type 2 immune response in peripheral blood from patients with asthma
TL;DR: Investigating whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and whether ILC2s are involved in human asthma suggested potential differences in the immunopathogenesis of these diseases.
Journal ArticleDOI
Cytokine and cytokine receptor pleiotropy and redundancy.
TL;DR: A range of different systems wherein cytokine receptor components are shared are summarized, discussing the implications thereof.
Journal ArticleDOI
IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development.
Michael J. Townsend,Padraic G. Fallon,David John Matthews,Philip Smith,Helen E. Jolin,Andrew N. J. McKenzie +5 more
TL;DR: Deletion of IL-9 manifests as a highly defined phenotype in Th2 responses modulating mucus production and mast cell proliferation in response to lung challenge.
Journal ArticleDOI
A Randomized, Controlled, Phase 2 Study of AMG 317, an IL-4Rα Antagonist, in Patients with Asthma
Jonathan Corren,William W. Busse,Eli O. Meltzer,Lyndon E. Mansfield,George W. Bensch,John Fahrenholz,Sally E. Wenzel,Yun Chon,Meleana Dunn,Haoling H. Weng,Shao-Lee Lin +10 more
TL;DR: Clinically significant improvements were observed in several outcome measures in patients with higher baseline ACQ scores, and AMG 317 did not demonstrate clinical efficacy across the overall group of patients.
References
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TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
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Douglas S. Robinson,Qutayba Hamid,Sun Ying,Anne Tsicopoulos,J. Barkans,Andrew Bentley,Christopher Corrigan,Stephen R. Durham,A. B. Kay +8 more
TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
Journal ArticleDOI
Eosinophilic inflammation in asthma.
Jean Bousquet,Pascal Chanez,J.-Y. Lacoste,G. Barneon,N Ghavanian,I. Enander,Per Venge,Staffan Ahlstedt,J Simony-Lafontaine,P. Godard +9 more
TL;DR: Eosinophilic inflammation of the airways is correlated with the severity of asthma and these cells are likely to play a part in the epithelial damage seen in this disease.
Journal ArticleDOI
Requirement for IL-13 Independently of IL-4 in Experimental Asthma
Gabriele Grünig,Martha L. Warnock,Adil E. Wakil,Rajeev Venkayya,Frank Brombacher,Donna M. Rennick,Dean Sheppard,Markus Mohrs,Debra D. Donaldson,Richard M. Locksley,David B. Corry +10 more
TL;DR: This article showed that IL-4 receptor α chain-dependent pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL4 receptor and showed that selective neutralization of IL-13, a cytokine related to interleukin-4 that also binds to the α chain of the IL 4 receptor, ameliorated asthma phenotype.
Journal ArticleDOI
Cellular events in the bronchi in mild asthma and after bronchial provocation.
TL;DR: It is concluded that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.
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