Prostaglandin E2 mediates activation of hypothalamic histamine by interleukin-1beta in rats.

Abstract

The present study was designed to investigate the effects of peripheral interleukin-1beta (IL-1beta) on hypothalamic histamine (HA) systems. Intraperitoneal injection of IL-1beta increased the turnover rate of hypothalamic HA, which was assessed by accumulation of tele-methylhistamine after pargyline treatment. IL-1beta increased the activities of both histidine decarboxylase (HDC), an HA synthesizing enzyme, and HA-N-methyltransferase (HMT), an HA catabolizing enzyme. Pretreatment with indomethacin completely blocked the effects induced by IL-1beta on hypothalamic HA. Infusion of prostaglandin E2 (PGE2) into the third cerebroventricle increased the hypothalamic HA turnover rate, and simultaneously activated both HDC and HMT dose-dependently, but intravenous infusion of PGE2 had no effect on the dynamics of hypothalamic HA turnover. These results indicate that hypothalamic PGE2 activated by peripheral administration of IL-1beta, but not by peripheral PGE2, may enhance synthesis and release of hypothalamic HA by activation of HDC, and may facilitate degradation of extracellular histamine by activation of HMT.