Dexamethasone inhibits the pyrogenic activity of prostaglandin F2 alpha, but not prostaglandin E2.
The effect of dexamethasone on prostaglandin (PG) E2- and PGF2 alpha-induced fever was studied in rats. Intracerebroventricular injection of PGE2 and PGF2 alpha (500 ng) induced increases in body temperature (maximal temperature rises of 0.97 +/- 0.13 degrees C and 0.78 +/- 0.18 degrees C, respectively, vs. vehicle 0.12 +/- 0.09 degrees C) of unrestrained rats maintained within the thermoneutral zone. PGE2-induced fever peaked earlier and the defervescence was faster when compared to the response induced by PGF2 alpha. Subcutaneous pre-administration of dexamethasone (0.5 mg/kg) did not affect PGE2-induced fever (maximal temperature rise of 1.00 +/- 0.08 degrees C), but completely prevented the pyrogenic activity of PGF2 alpha (maximal temperature rise of 0.16 +/- 0.16 degrees C). Neither PGE2- nor PGF2 alpha-induced fever was significantly altered (maximal temperature rises of 0.90 +/- 0.11 degrees C and 0.64 +/- 0.14 degrees C, respectively) by intraperitoneal administration of indomethacin (2 mg/kg). These results demonstrate for the first time that glucocorticoids, in addition to inhibiting endotoxin- and cytokine-induced fever, can also modulate the pyrogenic activity of some prostaglandins, possibly via suppression of the synthesis of corticotropin-releasing factor, indicating that multiple mechanisms may be involved in the antipyretic activity of these steroids.
Coelho
M M
MM
Department of Physiological Sciences, University of Manchester, UK.
Pelá
I R
IR
Rothwell
N J
NJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D015237:Dinoprost / Q000037:antagonists & inhibitors*; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy*; D007213:Indomethacin / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D011749:Pyrogens / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011749:Pyrogens; D003907:Dexamethasone; D015237:Dinoprost; D015232:Dinoprostone; D007213:Indomethacin