Dexamethasone fails to produce antipyretic and analgesic actions in experimental animals

Abstract

In order to explore the role of phospholipase A₂ inhibition in the mechanisms of the action of glucocorticoids, it was investigated whether the steroid exhibits the analgesic and antipyretic actions as well as cyclo-oxygenase inhibitors such as indomethacin or not. Dexamethasone has been reported to produce the anti-inflammatory action with a lag time of at least 1 h at doses of up to 0.1 mg/kg in mice and rats. However, dexamethasone when given 4 h beforehand had no significant analgesic, activity even at doses of 1 and 10 mg/kg i.v. in the acetic acid writhing test in rats. In mice, the significant reduction in writhes counts was seen when dexamethasone (1 and 10 mg/kg i.v.) was given 15 min or 4 h before phenylquinone injection; i.e. the activity had not the lag time. On the other hand, dexamethasone showed a strong antipyretic activity against both the fevers caused by LPS and yeast in rats. In the yeast-febrile rats, the antipyretic activity had a lag time of about 1 h, and was dose-related at doses as low as 0.03 to 0.3 mg/kg i.v.; the steriod markedly reduced the increased PGE₂ content in the cerebrospinal fluid. The antipyretic activity after local injection into the cerebroventricle or the yeast pouch was stronger than that after systemic injection into the tail vein, although so large a difference in the activity between the dosage routes was not seen, suggesting that the site of the antipyretic action is in both the brain and periphery. The antipyretic activity of dexamethasone (10 mg/kg i.v.) was not seen in rabbits with fever caused by LPS. These results suggest that dexamethasone failed to produce the clear analgesic and antipyretic actions. The relation of the present result to the phospholipase A₂ inhibition by the steroid was discussed.