Potential Therapeutic Aspects of Alarmin Cytokine Interleukin 33 or Its Inhibitors in Various Diseases

Purpose: The purpose of this review was to examine the comprehensively accumulated data regarding potential therapeutic aspects of exogenous administration of interleukin 33 (IL-33) or its antagonists in allergic, cancerous, infectious, and inflammatory diseases. Methods: A selected review was undertaken of publications that examined the protective and exacerbating effects of IL-33 or its inhibitors in different diseases. Mechanisms of action are summarized to examine the putative role of IL-33 in various diseases. Findings: IL-33 promoted antibacterial, antiviral, anti-inflammatory, and vaccine adjuvant functions. However, in T(H)2-biased respiratory, allergic, parasitic, and inflammatory conditions, IL-33 exhibited disease-sensitizing effects. The alarmin cytokine IL-33 induced protective effects in diseases via recruitment of regulatory T cells; antiviral CD8(+) cells, natural killer cells, gamma delta T cells, and nuocytes; antibacterial and antifungal neutrophils or macrophages; vaccine-associated B/T cells; and inhibition of nuclear factor kappa B-mediated gene transcription. In contrast, IL-33 exacerbated the disease process by increasing T(H)2 cytokines, IgE and eosinophilic immune responses, and inhibition of leukocyte recruitment in various diseases. Implications: The protective or exacerbated aspects of use of IL-33 or its inhibitors are dependent on the type of infection or inflammatory condition, duration of disease (acute or chronic), organ involved, cytokine microenvironment, dose or kinetics of IL-33, and genetic predisposition. The alarmin cytokine IL-33 acts at cellular, molecular, and transcriptional levels to mediate pluripotent functions in various diseases and has potential therapeutic value to mitigate the disease process. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.