Overview of the interleukin-1 family of ligands and receptors

This issue of Seminars in Immunology on The Interleukin-1 (IL-1) Family of Ligands and Receptors updates the rapidly expanding importance of this family. There are individual chapters on IL-1α, IL-1β, processing and secretion of IL-1β, IL-18, IL-33, IL-36 and IL-37. In addition, a chapter of IL-1 decoy receptors, IL-1 signaling receptors and the clinical applications of IL-1 blockade in human disease is included. More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of IL-1 family of receptors contains a domain, which highly homologous to the cytoplasmic domains of all Toll like receptors (TLR). This domain is termed Toll IL-1 receptor (TIR) domain and mutations in the TIR of IL-1 receptors or TLR abrogates signal transduction. Thus, fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. Both TLR and IL-1 families non-specifically affect antigen recognition and lymphocyte function, and therefore act as helpers (adjuvants) for specific immune responses, now called acquired immunity. IL-1β is the most studied member of the IL-1 family due to its role in mediating auto-inflammatory disease. Although the TLR and IL-1 families evolved to assist host defense against infection, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also non-specifically for TLR ligands and the innate immune response.