Me. Sisson et al., SUPPRESSION OF POKEWEED MITOGEN-DRIVEN HUMAN-IGM AND IGG RESPONSES BYTHE HYDROXYLAMINE OF SULFAMETHOXAZOLE, International journal of immunopharmacology, 19(5), 1997, pp. 299-304
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.