Depolarization and a NO-donor stimulate interleukin-1 beta release from the rat hypothalamus via a mechanism involving caspase 1

Previous in vitro studies showed that rat hypothalamic explants release int erleukin-1 beta (IL-1 beta); such release is significantly increased by sev eral stimuli including 56 mM KCl and NO-donors in 20-min experiments. Here we tested the hypothesis that the above stimuli act via a mechanism involvi ng cleavage of the IL-1 beta precursor by interleukin-1 beta converting enz yme (ICE, also referred to as caspase-1). A cell-permeable form of the casp ase-1 inhibitor I acid two different stimuli, 56 mM KCl and sodium nitropru sside (SNP), were used. The inhibitor was able to counteract the increase i n IL-1 beta release induced by both K+ and SNP, while having no effect on b asal release. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.