PGE2 receptor subtype EP1 antagonist may inhibit central interleukin-1beta-induced fever in rats

We have previously reported that central injection of PGE2 induces hyperthermia through its actions on EP1 receptors in rats. Because the increase in local synthesis of PGE2 is assumed to be a necessary process in a fever caused by central injection of interleukin-1beta (IL-1beta), an EP1 receptor antagonist (SC-19220) should inhibit the IL-1beta-induced fever. To test this hypothesis, we observed the effect of SC-19220 on the fever produced by injection of recombinant human IL-1beta (rhIL-1beta) into the lateral cerebroventricle (LCV) in conscious rats. Administration of SC-19220 (100 microgram) into the LCV 15 min before LCV injection of rhIL-1beta (4 ng) suppressed an initial rise in colonic temperature for 30 min, producing a fever with a longer latency to onset and a longer time to peak elevation. SC-19220, given 60 min after the central administration of rhIL-1beta, also suppressed the rhIL-1beta-induced fever 15-60 min after its injection. These findings suggest that the central IL-1beta-induced fever in rats is mediated, at least partly, by activation of EP1 receptors by PGE2.