Effects of sulfamethoxazole and trimethoprim on human neutrophil and lymphocyte functions in vitro: in vivo effects of co-trimoxazole

Abstract

The effects of sulfamethoxazole and trimethoprim individually and in combination on in vitro neutrophil random migration, chemotaxis to autologous endotoxin-activated serum and the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, phagocytosis and postphagocytic Nitro Blue Tetrazolium reduction, glycolysis, hexose monophosphate shunt activity, myeloperoxidase-mediated protein iodination, hydrogen peroxide production, and degranulation were assessed. The effects on lymphocyte mitogen-induced transformation were also evaluated. It was found that the test agents individually and in combination at high concentrations (> 100 microgram/ml) caused the inhibition of neutrophil postphagocytic myeloperoxidase-mediated protein iodination, which was related to the interference with H2O2 formation as the enzyme per se was unaffected. Both agents caused the inhibition of lymphocyte transformation at high concentrations (> 100 microgram/ml). In vivo studies before and after the ingestion of co-trimoxazole by three individuals showed no inhibition of any of the neutrophil functions tested. The inhibition of lymphocyte transformation was observed in one individual after the ingestion of the chemotherapeutic agent. These findings indicate that the concentrations which inhibit neutrophil H2O2 production and lymphocyte transformation in vitro are not attainable in vivo.