Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits.

Abstract

SUMMARY1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration.2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546.3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1.4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic.

Intraventricular microinjections of a stable analogue of prostaglandin endoperoxide cause fever in rabbits.

“…This is consistent with the idea that prostaglandin is the faster acting pyrogenic derivative of arachidonic acid (Laburn et al 1977). The origin of the latency of response to endoperoxide remains unknown.…”

“…Cranston et al (1975) showed that raised concentrations of prostaglandin E in the cerebrospinal fluid of rabbits was not a necessary accompaniment to fever, and more recent work (Cranston et al 1976) has shown that leucocyte pyrogen fever is unaffected by the simultaneous intraventricular injection of either of two prostaglandin antagonists, but that prostaglandin E2 fever is effectively attenuated by these antagonists. Laburn et al (1977) have shown that the pyrexia following sodium arachidonate injection is also unaffected by simultaneous administration of prostaglandin antagonists. Moreover the sodium arachidonate pyrexia was brought about by derivatives of arachidonic acid which are pyrogenic.…”

“…Control experiments consisted of similar injections of 28 n-mole of the prostaglandin endoperoxide analogue with 10 #I. ethanol. Intraventricular injections of indomethacin alone have been shown previously to have no effect on the rectal temperatures of rabbits for 2-5 h following injection, and thereafter a slight hyperthermic effect (Laburn et al 1977).…”

Effects of Intracerebroventricular Floctafenine and Indomethacin on Body Temperature in Febrile Rabbits

“…The antipyretic action of indomethacin does not depend on the alcohol vehicle. We have previously shown intraventricular injections of indomethacin to be antipyretic when the vehicle is dimethyl sulphoxide (Laburn, Mitchell & Rosendorff, 1977). …”

Communications

“…Although there is circumstantial evidence implicating E prostaglandins as mediators in the genesis of fever, critical testing of the hypothesis has failed to provide confirmation (Hellon, 1978). An alternative explanation is that metabolites of arachidonic acid other than prostaglandins might act as mediators of fever (Laburn, Mitchell & Rosendorff, 1977). The protein synthesis inhibitor, cycloheximide, is known to abolish the febrile response to intravenous injection of leucocyte pyrogen without affecting the elevation in c.s.f.…”