Role of interleukin-18 in the pathophysiology of allergic diseases

Abstract

Interleukin (IL)-18 is an IL-1 family cytokine expressed by macrophages, dendritic cells, epithelial cells, and keratinocytes and is implicated in various aspects of both the innate and adaptive immune systems. IL-18 signals similar to IL-1β intracellularly to activate gene transcription. Since its discovery, IL-18 has been demonstrated to play a key role in pathogen defense from helminths and some bacteria. Recently however, evidence has accumulated that IL-18 expression is increased in many presentations of allergic disease. A pathologic role for IL-18 includes stimulating mast cell and basophil degranulation, recruiting granulocytes to sites of inflammation, increasing cytotoxic activity of natural killer (NK) and NK-T cells, inducing Immunoglobulin (Ig)E production and isotype switching, and affecting a broad range of T cells to promote a type II helper T cell (Th2) response. Evidence and importance of these effects are presented, including novel results from our lab implicating IL-18 in the direct expansion of mast cells, basophils, and other myeloid-lineage cells from bone-marrow precursors. The development of urticaria, asthma, dermatitis, rhinitis, and eosinophilic disorders all have demonstrated correlations to increased IL-18 levels either in the tissue or systemically. IL-18 represents a novel site of immune regulation in not only allergic conditions, but also autoimmune diseases and other instances of aberrant immune functioning. Diagrammatic summarized abstract for readers convinance is presented in Fig. 1.

Keywords: Allergy; Eosinophils; Interleukin-18; Mast cells; iNKT cells.

Figure 1. Abstract Summary

Diagrammatic presentation of review summary on IL-18 secretion by the epithelial and antigen presenting cells and its role in promoting allergic and autoimmune diseases by activating inflammatory cells.

Figure 2. Diagrammatic representation of IL-18 involvement in innate and adaptive immunity

Pro-inflammatory pathway of IL-18 in the maturation and activation of T cell subsets are demonstrated by red arrows and anti-inflammatory pathway by green arrows, and blue arrows indicates that IL-18 has a role in a number of inflammatory cells activation to promote autoimmune and allergic diseases. The presented summary indicates that IL-18 is involved in natural killer T cells activation, induces B cell differentiation, and conversion of naïve T cells to Th2 cells. IL-18 can stimulate the conversion in vitro of Th1 cells to “super Th1 cells” that produce Th2 cytokines that promotes autoimmune and allergic diseases and in synergy with IL-12 activates T regulatory cell activity and Th1 cytokine to release anti-inflammatory cytokines.