Production of tumour necrosis factor by cells exposed to sulphonamide reactive metabolites.
Hypersensitivity reactions are the most common adverse events associated with therapy with the sulphonamide antibiotics. These reactions have been shown to occur among individuals with pharmacogenetically determined differences in the capacity of their cells to detoxify reactive products of oxidative metabolism of the sulphonamides. These reactions appear to be propagated by an inflammatory response by the immune system. To investigate the role of the cytokine tumour necrosis factor (TNF-alpha) in these reactions, we studied the production of TNF-alpha by peripheral blood mononuclear cells (PBMCs) that had been incubated with sulfamethoxazole and murine microsomes in the presence and absence of a microsomal-activating system and TNF-alpha production by PBMCs in the presence and absence of the hydroxylamine derivative of sulfamethoxazole. The PBMCs showed a time-related increase in the production of TNF-alpha. There was no increase in TNF-alpha production seen during incubation with sulphonamide reactive metabolites; rather, there was a decrease in TNF-alpha elaboration that was most marked when PBMCs were incubated with the hydroxylamine of sulfamethoxazole. There is no evidence from these in vitro studies that TNF-alpha is involved as a mediator of the inflammatory response in sulphonamide hypersensitivity adverse drug reactions.
Rieder
M J
MJ
Department of Paediatrics, University of Western Ontario, London, Canada.
Mask
M
M
Bird
I A
IA
D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004342:Drug Hypersensitivity / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D051379:Mice; D009000:Monocytes / Q000276:immunology; D013449:Sulfonamides / Q000378:metabolism / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha