Inhibitory effect of TI-31 on autoimmune nephritis in NZB/NZW F1 mice through regulation of the immune response.

TI-31 (TEI-3096; 6-p-chlorobenzyl-5H-2,3,6,7-tetrahydro-5,7-dioxothiazolo[3,2-a]pyr imidine) is a novel immunomodulator. Various nephritic changes observed in female NZB/NZW F1 (B/W) mice with aging were suppressed by TI-31 when administered orally 5 times per week for 16 weeks at doses of 2, 10, or 50 mg/kg. It suppressed proteinuria, oliguria, the decrease of erythrocyte count, and increase of serum urea nitrogen, immune complex and anti-double-stranded DNA antibody levels. The anti-nephritic effect of TI-31 was confirmed by histopathological evaluation. TI-31 (10 mg/kg) could improve both the elevated polyclonal B cell activation and the depressed antibody response to sheep red blood cells in B/W mice, in comparison with age- and sex-matched BALB/c mice, without any effect on the antibody response in these normal mice. These findings indicate that TI-31 may inhibit B/W nephritis by regulating the antibody production through a mechanism different from that of anti-inflammatory drugs or immunosuppressants.