DEXAMETHASONE INHIBITS THE PYROGENIC ACTIVITY OF PROSTAGLANDIN-F(2-ALPHA), BUT NOT PROSTAGLANDIN-E2

The effect of dexamethasone on prostaglandin (PG) E2- and PGF2alpha-in duced fever was studied in rats. Intracerebroventricular injection of PGE and PGF2alpha (500 ng) induced increases in body temperature (maxi mal temperature rises of 0.97 +/- 0.13-degrees-C and 0.78 +/- 0.18-deg rees-C, respectively, vs. vehicle 0.12 +/- 0.09-degrees-C) of unrestra ined rats maintained within the thermoneutral zone, PGE2-induced fever peaked earlier and the defervescence was faster when compared to the response induced by PGF2alpha. Subcutaneous pre-administration of dexa methasone (0.5 mg/kg) did not affect PGE2-induced fever (maximal tempe rature rise of 1.00 +/- 0.08-degrees-C), but completely prevented the pyrogenic activity of PGF2alpha (maximal temperature rise of 0.16 +/- 0.16-degrees-C). Neither PGE2- nor PGF2alpha-induced fever was signifi cantly altered (maximal temperature rises of 0.90 +/- 0.11-degrees-C a nd 0.64 +/- 0.14-degrees-C, respectively) by intraperitoneal administr ation of indomethacin (2 mg/kg). These results demonstrate for the fir st time that glucocorticoids, in addition to inhibiting endotoxin- and cytokine-induced fever, can also modulate the pyrogenic activity of s ome prostaglandins, possibly via suppression of the synthesis of corti cotropin-releasing factor, indicating that multiple mechanisms may be involved in the antipyretic activity of these steroids.