Effects of tilomisole, indomethacin and levamisole on regulation of Epstein Barr virus-induced B cell proliferation by peripheral blood mononuclear cells from normal individuals and patients with rheumatoid arthritis.

Abstract

When activated in autologous mixed leukocyte reactions (auto-MLR) in vitro, T cells from normal individuals produce a suppressor factor(s) which inhibits the Epstein-Barr virus (EBV)-induced proliferation of normal B cells. In contrast, T cells from patients with rheumatoid arthritis (RA) are deficient in their ability to generate this suppressor factor in auto-MLR. Addition of tilomisole (Wy-18,251; 33(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) to the auto-MLR (0.1-100 micrograms/ml) did not alter the production of suppressor activity by normal T cells, but 100 micrograms/ml tilomisole restored to normal the defective factor production by RA T cells. Indomethacin (1 microgram/ml) but not levamisole (0.1-100 micrograms/ml) had a similar effect, which suggests that the action of tilomisole in this system is due to its ability to inhibit prostaglandin biosynthesis. Nonetheless, the ability of tilomisole to down-regulate B cell function may contribute to the compound's antiarthritic activity.