Cloning of rat brain interleukin-18 cDNA

Abstract

The interleukin-1 (IL-1) family comprises IL-1α and IL-1β 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-1α nor IL-1β are neurotoxic per se in vivo, so other IL-1 related ligands may be important in neurodegeneration. The cytokine interleukin-18 (also called interferon gamma inducing factor, IGIF) was first isolated from the liver 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-1β and IL-1ra, and has tentatively been called IL-1γ.⁴ We cloned IL-18 from adult rat brain and demonstrated, by RT-PCR, that it is expressed constitutively in cerebellum, hippocampus, hypothalamus, cortex and striatum. Rat brain IL-18 shows close homology to mouse³ and human IL-18,⁵ and to the recently published sequence from the rat adrenal gland.⁶ Mouse pro-IL-18 and pro-IL-1β are processed by caspase-1.^7,8 We demonstrate that caspase-1 also cleaves rat IL-18 in vitro and that the caspase inhibitor, zVAD-DCB inhibits this cleavage.