OVERVIEW OF INTERLEUKIN-18 - MORE THAN AN INTERFERON-GAMMA INDUCING FACTOR

Initially described in 1989 as interferon-gamma (IFN-gamma) inducing f actor (IGIF), interleukin-18 (IL-18) is a novel pro-inflammatory-cytok ine that is clearly more than an inducer of IFN-gamma, The cytokine po ssesses several biological properties such as activation of nuclear fa ctor-kappa B (NF-kappa B), Fas ligand expression, the induction of bot h CC and CSC chemokines, and increased production of competent human i mmunodeficiency virus. Most activities are due to a receptor complex t hat recruits the IL-1 receptor-activating kinase (IRAK), leading to tr anslocation of NF-kappa B, This property and others support the concep t that IL-18 is related to the IL-1 family, Indeed, one of the 1L-18 r eceptor chains is the IL-1 receptor-related protein, a member of the I L-1R family. In addition, IL-18 is structurally similar to IL-1 beta a nd like IL-1 beta is first synthesized as a leaderless precursor requi ring the IL-1 beta converting enzyme for cleavage into an active molec ule. The biology of IL-18 is reviewed in the overview and the implicat ion for a role for this cytokine in disease is presented.