EFFECT OF ENDOTOXIN AND INTERLEUKIN-1-BETA ON CORTICOTROPIN-RELEASINGFACTOR AND PROSTAGLANDIN RELEASE BY RAT BRAIN-STEM SLICES

This study investigated the effects of lipopolysaccharide (LPS) and in terleukin-1 beta (IL-1 beta) on corticotropin releasing factor (CRF) a nd prostaglandin E-2 (PGE(2)) release by brainstem slices in vitro. Fi rst, we characterized our experimental model and demonstrated that hig h potassium stimulates CRF release from rat brainstem slices in a calc ium dependent way. The direct stimulation of brainstem slices with IL- 1 beta (3-25 pM) did not modify basal or potassium-stimulated CRF rele ase, although IL-1 beta at the dose of 25 pM increased PGE(2) producti on. Peripheral injection (ip) of LPS (1-10 mu g/kg) or IL-1 beta (1-10 mu g/kg) evoked a dose-related potentiation of the ex-vivo release of CRF and PGE(2) from brainstem slices, However, central (icv) administ ration of LPS (10-500 ng/rat) potentiated the release of CRF and PGE(2 ) only at the dose of 500 ng/rat, whereas IL-1 beta (1-100 ng/rat) fai led to modify significantly the ex vivo production of both CRF and PGE (2). The results of the present study provide evidence that peripheral , rather than central, endotoxin and IL-1 beta administration induce t he activation of brainstem CRF and PGE(2), supporting the hypothesis t hat peripheral cytokine signalling to the CNS is mediated by stimulati on of peripheral afferents.