Interleukin-18

Interleukin (IL)-18 is a newly discovered cytokine, structurally similar to IL-1, with profound effects on T-cell activation. This short review summar izes the present knowledge on IL-18, to give an insight into the future per spectives for its possible use as vaccine adjuvant. Formerly called interfe ron (IFN) gamma inducing factor (IGIF), IL-18 is the new name of a novel cy tokine that plays an important role in the T-cell-helper type 1 (Th1) respo nse, primarily by its ability to induce IFN gamma production in T cells and natural killer (NK) cells. Mice deficient in IL-18 have suppressed IFN gam ma production despite the presence of IL-12 IL-18 is related to the IL-1 fa mily in terms of structure, receptor family, and function. In terms of stru cture, IL-18 and IL-1 beta share primary amino acid sequences of the so-cal led "signature sequence" motif a:nd are similarly folded as all-P pleated s heet molecules. Also similar to IL-1 beta, IL-18 is synthesized as a biolog ically inactive precursor molecule lacking a signal peptide which requires cleavage into an active, mature molecule by the intracellular cysteine prot ease called IL-1 beta-converting enzyme (ICE, also called caspase-1). The a ctivity of mature IL-18 is closely related to that of IL-1. IL-18 induces g ene expression and synthesis of tumor necrosis factor (TNF), IL-1, Fas liga nd, and several chemokines. The activity of IL-18 is via an IL-18 receptor (IL-18R) complex. This IL-18R complex is made up of a binding chain termed IL-18R alpha, a member of the IL-1 receptor family previously identified as the IL-1 receptor-related protein (IL-1Rrp), and a signaling chain, also a member of the IL-1R family. The IL-18R complex recruits the IL-1R-activati ng kinase (IRAK) and TNFR-associated factor-6 (TRAF-6) which phosphorylates nuclear factor kappa B (NF kappa B)-inducing kinase (NIK) with subsequent activation of NF kappa B. Thus on the basis of primary structure, three-dim ensional structure, receptor family, signal transduction pathways and biolo gical effects, IL-18 appears to be a new member of the IL-1 family. Similar to IL-1, IL-18 participates in both innate and acquired immunity. (C) 1999 Academic Press.