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.
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.
Gilman
S C
SC
Division of Experimental Therapeutics, Wyeth Laboratories, Inc., Philadelphia, PA 19101.
Bluestein
H G
HG
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001562:Benzimidazoles / Q000494:pharmacology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007978:Levamisole / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*
D001562:Benzimidazoles; D007978:Levamisole; C029171:tilomisole; D007213:Indomethacin