Role of interleukin-18 in the pathophysiology of allergic diseases.

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.