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Dexamethasone inhibits the pyrogenic activity of prostaglandin F2 alpha, but not prostaglandin E2.
Coelho M, Pelá I, Rothwell NJ
Eur J Pharmacol. 1993;238(2-3):391-394.
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Abstract
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.
Keyword(s)
Animals; Comparative Study; Injections, Subcutaneous; Male; Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't; antagonists & inhibitors: Dinoprost; antagonists & inhibitors: Dinoprostone; antagonists & inhibitors: Pyrogens; chemically induced: Fever; drug effects: Body Temperature; pharmacology: Dexamethasone; pharmacology: Indomethacin