LONG-TERM TREATMENT WITH 5,5-DIPHENYLHYDANTOIN REDUCES LYMPHADENOPATHY AND ANTI-SSDNA AUTOANTIBODIES IN C57BL 6 LPR/LPR MICE/

To further the insight in the immunomodulating properties of the antic onvulsant 5,5-diphenylhydantoin (DPH), C57BL/6 (B6), C57BL/6-lpr/lpr ( B6-lpr/lpr) and MRL/MpJ-+/+ (MRL) mice received DPH orally for six mon ths to determine weekly urinary biopterin levels, a potential T-cell a ctivation marker, by high performance liquid chromatography. At the en d of the experiment serum antibody levels were measured by ELISA and r elative lymphoid organ weights determined. DPH treatment resulted in r educed body weight in all strains, reduced spleen weights in B6 and MR L mice, profoundly reduced popliteal lymph node weights in B6-lpr/lpr mice and increased thymus weights in MRL mice. DPH treatment decreased serum IgM, IgG and IgA as well as IgM and IgG anti-ssDNA levels in B6 -lpr/lpr mice, but did not affect these parameters in other strains. E ffects of DPH on IgM rheumatoid factor levels in B6Ipr/lpr mice were i nconsistent. Urinary biopterin levels of untreated B6 and B6-lpr/lpr m ice were about equal and lower than those of MRL mice. During the firs t three months of DPH treatment, persistently elevated biopterin level s were observed in B6 and to a lesser degree in MRL mice, and alternat ely elevated and control levels in B6-lpr/lpr mice. Thereafter, the ef fects faded in all strains. Results show that long-term DPH treatment causes only minor lymphoid organ weight changes in B6 and MRL mice, bu t causes a clear reduction of the lymphadenopathy and (auto)antibody f ormation in B6-lpr/lpr mice. Observed changes could not be related to altered biopterin excretion indicating that the latter is an inappropr iate marker of murine autoimmune disease.