PGE₂ receptor subtype antagonist may inhibit central interleukin-1β- 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-1β (IL-1β), an EP₁ receptor antagonist (SC-19220) should inhibit the IL-1β-induced fever. To test this hypothesis, we observed the effect of SC-19220 on the fever produced by injection of recombinant human IL-1β (rhIL-1β) into the lateral cerebroventricle (LCV) in conscious rats. Administration of SC-19220 (100 μg) into the LCV 15 min before LCV injection of rhIL-1β(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-1β, also suppressed the rhIL-1β-induced fever 15-60 min after its injection. These findings suggest that the central IL-1β-induced fever in rats is mediated, at least partly, by activation of EP₁ receptors by PGE₂.