Suppression of pokeweed mitogen-driven human IgM and IgG responses by the hydroxylamine of sulfamethoxazole

Abstract

Objective: To determine the effect(s) of reactive sulfonamide metabolites on antibody production by human lymphocytes. Methods: Human peripheral blood cells (PBMCs) were isolated from control volunteers and incubated with the hydroxylamine of sulfamethoxazole (SMX H/A), a reactive metabolite of the most commonly used sulfonamide, in increasing concentrations. PBMCs were then stimulated to produce antibody with pokeweed mitogen. After incubation for 8 days, concentrations of IgG and IgM were determined in supernatant using an ELISA assay. Results: Production of both IgG and IgM was significantly suppressed by sub-lethal concentrations 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 decline to 57% of baseline antibody production). No suppresion was seen when cells were incubated with sulfamethoxazole in concentrations up to 400 μM. This suppression was not related to changes in cell viability; at a concentration of 25 μM of SMX H/A, IgM and IgG concentration were reduced by 47±8.7% and 73±7.2%, while cell viability (percentage 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 concentrations which are achieved during therapy, suppress antibody production by PWM-stimulated human cells. This may explain, in part, the alterations in immunity associated with hypersensitivity reactions to the sulfonamides. This may also have implications for patients receiving sulfonamide therapy and concurrent immunosuppressive therapy.