INTERLEUKIN-1BETAINCREASES PROSTAGLANDIN E2IN RAT ASTROCYTE CULTURES: MODULATORY EFFECT OF NEUROPEPTIDES

Abstract

Recombinant human interleukin-1 beta (IL-1.beta.) significantly increased prostaglandin E2 (PGE2) in a dose-dependent manner in rat astrocyte culture. The minimum effective dose of IL-1.beta. was 10-10M. IL-1.alpha. also increased GE2, but at a higher concentration. The minimum effective dose of IL-1.alpha. was 10-8M, indicating it to be 100-fold less effective than IL-1.beta.. On the other hand neither iL-1.beta. nor IL-1.alpha. increased PGE2 production by neuron cultures at any concentration tested. PGE2 response to IL-1.beta. was suppressed by simultaneous addition of CRH, somatostatin-14 and LHRH, while these neuropeptides alone did not alter the basal PGE2 levels. Substance P, vasoactive intestinal polypeptide and .alpha.-MSH altered neither basal nor IL-1.beta.-induced increase in PGE2 levels. Angiotensin II (AII) alone also increased PGE2 incultured astrocytes. Combined addition of AII and IL-1.beta. induced a synergistic effect in increasing PGE2 levels. The direct actin of IL-1.beta. on astrocyte culture suggests that astrocytes may be the target cells for IL-1.beta. in the central nervous system. In view of the essential role of central PGE2 in IL-1.beta.-induced CRH/ACTH release, these findings suggest the presence of a sophisticated regulatory network in the immune-neuroendocrine interaction.