SUPPRESSION OF POKEWEED MITOGEN-DRIVEN HUMAN-IGM AND IGG RESPONSES BYTHE HYDROXYLAMINE OF SULFAMETHOXAZOLE

Objective: To determine the effect(s) of reactive sulfonamide metaboli tes on antibody production by human lymphocytes. Methods: Human periph eral blood cells (PBMCs) were isolated from control volunteers and inc ubated with the hydroxylamine of sulfamethoxazole (SMX H/A), a reactiv e metabolite of the most commonly used sulfonamide, in increasing conc entrations. PBMCs were then stimulated to produce antibody with pokewe ed mitogen. After incubation for 8 days, concentrations of IgG and IgM were determined in supernatant using an ELISA assay. Results: Product ion of both IgG and IgM was significantly suppressed by sub-lethal con centrations of SMX H/A in a concentration-dependent fashion (p<0.05). Suppression was more marked for IgM production (maximal decline to 80% of baseline antibody production) than For IgG production (maximal dec line to 57% of baseline antibody production). No suppresion was seen w hen cells were incubated with sulfamethoxazole in concentrations up to 400 mu M. This suppression was not related to changes in cell viabili ty; at a concentration of 25 mu M of SMX H/A, IgM and IgG concentratio n were reduced by 47 +/- 8.7% and 73 +/- 7.2%, while cell viability (p ercentage of live cells) was 93 +/- 5%. Suppression was time-dependent , increasing over the incubation periods to reach a plateau after 2 h of incubation. Conclusion: Sulfonamide reactive metabolites, in concen trations which are achieved during therapy, suppress antibody producti on by PWM-stimulated human cells. This may explain, in part, the alter ations in immunity associated with hypersensitivity reactions to the s ulfonamides. This may also have implications for patients receiving su lfonamide therapy and concurrent immunosuppressive therapy. (C) 1997 I nternational Society for Immunopharmacology.