Mechanism of the antipyretic effect of acetylsalicylic acid and salicylic acid in rabbits

To clarify the mechanisms of antipyretic effects of acetylsalicylic acid(ASA) and salicylic acid(SA), we prepared the sodium salts of both antipyretics(Na-ASA, Na-SA) and the effects were studied on fever induced with lipopolysaccharide (LPS), leucocytic pyrogen(LP) and 2, 4-dinitrophenol(DNP) in male adult rabbits. We obtained the following results.: After intravenous injection of Na-ASA or Na-SA, the biological half-life of both antipyretics was estimated to be 7 and 40 min, respectively, in plasma concentration of LPS-injected rabbits. The rectal temperature of normal rabbits remained unchanged after intravenous injection of Na-ASA (0.69 mmole/ kg, 140 mg/kg) or Na-SA (0.69 mmole/kg, 111 mg/kg). The most potent antipyretic effect was observed with intravenous injection of Na-ASA (140 mg/kg) at 0 or 2 hours after injection of LPS(0.2 μg/kg), while a weak effect was observed at 1 or 3 hours after LPS. Contrary to Na-ASA, the antipyretic effect was weakly or rarely observed with the injection of Na-SA (111mg/kg) at 1, 2 or 3 hours after LPS. The antipyretic effect of Na-ASA(140mg/kg) was observed in LP-induced fever with simultaneous injection, but no effect was seen with injection of Na-SA(111mg/kg). Intravenous injection of Na-ASA(140 mg/kg) or Na-SA(111mg/kg) did not suppress the fever induced with DNP (20 mg/kg, i.m.), but enhanced the fever. With intracisternal injection of Na-ASA(0.0035 mmole/kg), the antipyretic effect was markedly observed, but no effect was seen with Na-SA in LPS(0.2 μg/kg, i.v.)-induced fever. These results suggest that ASA may act on the central nervous system while SA may interfere with the production of LP in the peripheral system.