Effect of bacterial endotoxin and interleukin-1 on prostaglandin biosynthesis by the hippocampus of mouse brain: role of interleukin-1 receptors and glucocorticoids

There is increasing evidence indicating that the production of cytokines and prostaglandins (PG) may be interrelated and is regulated by glucocorticoids (GC). In the present study we examined the effect of the bacterial endotoxin lipopolysaccharide (LPS) and interleukin-1 (IL-1) on the ex vivo production of PGE2 by the dorsal hippocampus of the mouse which contains high levels of receptors to IL-1. The roles of IL-1 receptors and GC in the regulation of LPS- or IL-1-induced PGE2 production were also studied. In control mice the basal rate of PGE2 ex vivo synthesis by slices of dorsal hippocampus was about 250 pg/mg protein/60 min. Intraperitoneal injection of either LPS (1-50 micrograms/mouse) or IL-1 alpha (50-200 ng/mouse) increased the production of PGE2 in a dose-and time-dependent manner. Both LPS and IL-1 alpha induced a maximal 2.5-fold increase in PGE2 production at 6 h after the injections. IL-1 beta was less effective by approximately 30% as compared to IL-1 alpha. In mice treated with the IL-1 receptor antagonist or with the IL-1 antagonist alpha-melanocyte-stimulating hormone (alpha-MSH), the effects of LPS and IL-1 on PGE2 production were completely abolished. Intraperitoneal injections of dexamethasone (DEX) 5 or 30 micrograms/mouse 2 h prior to the administration of IL-1 alpha significantly enhanced the effect of the cytokine on PGE2 production. In mice treated with 100 micrograms DEX/mouse, the facilitatory effect of the lower DEX does in IL-1-induced PGE2 production was abolished.(ABSTRACT TRUNCATED AT 250 WORDS)