Abstract

Inflammation plays vital roles in protective responses against pathogens and tissue repair, however, improper resolution of inflammatory networks is centrally involved in the pathogenesis of many acute and chronic diseases. Extensive advances have been made in recent years to define the inflammatory processes that are required for pathogen clearance, however, in comparison, less is known about the regulation of inflammation in sterile settings. Over the past decade non-communicable chronic diseases that are potentiated by sterile inflammation have replaced infectious diseases as the major threat to global human health. Thus, improved understanding of the sterile inflammatory process has emerged as one of the most important areas of biomedical investigation during our time. In this review we highlight the central role that interleukin-1 family cytokines play in sterile inflammatory diseases.

Highlights

  • Infection and cellular injury are the two principal stimuli that provoke inflammation

  • In this review we focus on the roles of IL-1α, IL-1β, IL-18, and IL-33 in sterile inflammatory disease as these cytokines have been described to significantly influence disease pathogenesis

  • The effectiveness of IL-1 receptor (IL-1R) blockade in the treatment of Type 2 diabetes mellitus (T2DM) and other diseases suggest that additional therapeutics that target IL-1 family cytokines may provide effective strategies to treat other devastating inflammatory disorders

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Summary

Introduction

Infection and cellular injury are the two principal stimuli that provoke inflammation. Inflammatory responses play critical roles in the eradication of pathogens and sterile insults, excessive and unremitting inflammation causes damage to healthy tissue and centrally contributes to disease pathology. Sterile stimuli that trigger inflammasome activation include endogenous danger signals that are released during aberrant cell death (ATP and uric acid), metabolic factors (saturated fatty acids and cholesterol crystals), and exogenous irritants (asbestos and silica; Figure 2).

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