Effect of interferon synthesis upon the metabolism of [carboxyl-14C]-aspirin in the mouse

The effect of stimulation of interferon (IFN) synthesis with the immunomodulators, polyriboinosinic polyribocytidylic acid (poly rI:rC) and Newcastle Disease Virus (NDV) upon the in vivo metabolism of [carboxyl-14C]-aspirin was investigated in male mice of three different strains. Following poly rI:rC administration to DBA/2 mice, the metabolic conjugation of salicylic acid with glycine was significantly increased, glucuronidation was little changed and there was an approximately 10-fold reduction in the excretion of the oxidation product, gentisic acid. Prolongation of hexobarbitone-induced sleeping time confirmed the ability of this agent to depress oxidative metabolism in vivo. Poly rI:rC administration to C57BL/6By and BALB/cBy mice resulted in similar changes in aspirin metabolism in vivo. Treatment of C57BL/6By mice with NDV produced high levels of circulating IFN and produced alterations in aspirin metabolism similar to those seen after poly rI:rC treatment. Comparable studies in BALB/cBy mice, which did not produce detectable levels of IFN in response to NDV challenge, revealed no change in the fate of aspirin metabolism following treatment with this agent. These data indicate that the in vivo oxidation of salicylate, but not its conjugation, can be depressed, at least indirectly, by an interferon-associated mechanism.