Interleukin-33 in asthma: How big of a role does it play?

Asthma and Allergic Disease Center, Box 801355, University of Virginia Health Systems, Charlottesville, VA 22908-1355, USA.
Current Allergy and Asthma Reports (Impact Factor: 2.77). 10/2010; 11(1):7-11. DOI: 10.1007/s11882-010-0153-8
Source: PubMed


In complex disorders such as asthma and allergic disease, the goal for developing disease-modifying biotherapeutics is to find a target that is a central instigator of immunologic activity. Interleukin (IL)-33 seems to be such a molecule, as it is one of the earliest-released signaling molecules following epithelial damage and can orchestrate the recruitment and activation of the cells responsible for disease. Unregulated IL-33 activity leads to activation of T-helper type 2 cells, mast cells, dendritic cells, eosinophils, and basophils, ultimately leading to increased expression of cytokines and chemokines that define the disease. As such, IL-33 is an attractive candidate for therapeutic intervention with the goal of ameliorating disease. This review focuses on the role of IL-33 in promoting and maintaining the asthma phenotype.

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Available from: John W Steinke
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    • "Members of the IL-1 family play a critical role in the inflammatory responses. The best characterized members of this family include IL-1 α, IL-1 β, IL-1Ra, IL-18 and IL-33.[4950] IL-33 is expressed by many cells and tissues, including the stomach, brain, spleen, heart, bronchial epithelial cells, fibroblasts, smooth muscle cells, keratinocytes, macrophages and DCs.[51] "
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    ABSTRACT: Asthma is a reversible airway obstruction that is characterized by constriction of airway smooth muscle, hyper secretion of mucus, edema and airway hyper responsiveness (AHR), mucus secretion and thickening of the basement membrane underlying the airway epithelium. During the process of airway inflammation, complex interactions of innate and adaptive immune cells as well as structural cells and their cytokines have many important roles. It was believed that airway inflammation is orchestrated by allergen specific T helper (Th) 2 cells, which recruit and accumulate in the lungs and produce a range of different effector cytokines. However, more recent studies have revealed the potential collaboration of other helper T cells and their cytokines in this process. Th17 cell may have a role in severe asthma and chronic obstructive pulmonary disease (COPD). Interleukin (IL)-9-producing subset called Th9 cell, Th22 cells which primarily secrete IL-22, IL-13 and tumor necrosis factor-α and Th25 cells via producing IL-25 are believed to be important for initiating allergic reactions and developing airway inflammation. Cytokines are important in asthma and play a critical role in orchestrating the allergic inflammatory response, although the precise role of each cytokine remains to be determined. The aim of this review is to summarize the current knowledge about the possible roles of newly identified helper T cells derived cytokines (IL-9, 17, 22, 25 and IL-33) in asthma. The potential therapeutic applications emerging from the roles of these cytokines will be discussed as well.
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    • "Table 4). These data are in line with the accumulating evidence suggesting a role of IL33 in allergic mechanisms in asthma (Reviewed in [33]) although we cannot exclude that this is a false positive. Similarly, while not surviving correction, suggestive evidence for SNP associations for CRB1/BHR, IL18R/severity and IL33/SPT were apparent (p < 0.05), which may represent true associations. "
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    ABSTRACT: Asthma genome-wide association studies (GWAS) have identified several asthma susceptibility genes with confidence; however the relative contribution of these genetic variants or single nucleotide polymorphisms (SNPs) to clinical endpoints (as opposed to disease diagnosis) remains largely unknown. Thus the aim of this study was to firstly bridge this gap in knowledge and secondly investigate whether these SNPs or those that are in linkage disequilibrium are likely to be functional candidates with respect to regulation of gene expression, using reported data from the ENCODE project. Eleven of the key SNPs identified in eight loci from recent asthma GWAS were evaluated for association with asthma and clinical outcomes including percent predicted FEV1, bronchial hyperresponsiveness (BHR) to methacholine, severity defined by British Thoracic Society steps and positive response to skin prick test using the family based association test additive model in a well characterised UK cohort consisting of 370 families with at least two asthmatic children. GSDMB SNP rs2305480 (Ser311Pro) was associated with asthma diagnosis (p = 8.9x10-4), BHR (p = 8.2x10-4) and severity (p = 1.5x10-4) with supporting evidence from a second GSDMB SNP rs11078927 (intronic). SNPs evaluated in IL33, IL18R1, IL1RL1, SMAD3, IL2RB, PDE4D, CRB1 and RAD50 did not show association with any phenotype tested when corrected for multiple testing. Analysis using ENCODE data provide further insight into the functional relevance of these SNPs. Our results provide further support for the role of GSDMB SNPs in determining multiple asthma related phenotypes in childhood asthma including associations with lung function and disease severity.
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    • "Among injured structural cells, airway epithelium is having crucial importance as it is the primary barrier against exogenous and endogenous stress with its innate mechanisms. Recent literature demonstrated that airway epithelia can determine the immune status of lung by recruiting particular type of immune cells through its armamentarium of cytokines such as interlekin-25 (IL-25), IL-33 and thymic stromal lymphopoietin456. Due to these reasons current respiratory researchers have given a central role for airway epithelia in pathogenesis of lung diseases789. "
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