CLONING OF RAT-BRAIN INTERLEUKIN-18 CDNA

The interleukin-1 (IL-1) family comprises IL-1 alpha and IL-1 beta and an endogenous IL-1 receptor antagonist (IL-1ra).(1) IL-1 has diverse actions in the brain and has been implicated in both acute and chronic neurodegeneration.(1,2) However, neither IL-1 alpha nor IL-1 beta are neurotoxic per se in vivo, so other IL-1 related ligands may be impor tant in neurodegeneration. The cytokine interleukin-18 (also called in terferon gamma inducing factor, IGIF) was first isolated from the live r of mice during toxic shock.(3) It was later proposed as a member of the IL-1 family, based on protein sequence homology with IL-1 beta and IL-1ra, and has tentatively been called IL-1 gamma-(4) We cloned IL-1 8 from adult rat brain and demonstrated, by RT-PCR, that it is express ed constitutively in cerebellum, hippocampus, hypothalamus, cortex and striatum. Rat brain IL-18 shows close homology to mouse(3) and human IL18,(5) and to the recently published sequence from the rat adrenal g land.(6) Mouse pro-IL-18 and pro-IL-1 beta are processed by caspase-1. (7,8) We demonstrate that caspase-1 also cleaves rat IL-18 in vitro an d that the caspase inhibitor, zVAD-DCB inhibits this cleavage.