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; 3-(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) to the auto-MLR (0.1–100 μg/ml) did not alter the production of suppressor activity by normal T cells, but 100 μg/ml tilomisole restored to normal the defective factor production by RA T cells. Indomethacin (1 μg/ml) but not levamisole (0.1–100 μg/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.
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References
S. C. Gilman and A. J. Lewis,Immunomodulatory drugs in the treatment of rheumatoid arthritis. InAntiinflammatory and Antiarthritic Drugs. Vol. III, (Ed. K. D. Rainsford) pp. 127–153, CRC Press, Florida 1985.
P. A. Bardwick, H. G. Bluestein, N. J. Zvaifler, J. M. Depper and J. E. Seegmiller,Altered regulation of Epstein-Barr virus induced lymphoblast proliferation in rheumatoid arthritis lymphoid cells. Arthritis Rheum.23, 626–632 (1980).
F. Hasler, H. G. Bluestein, N. J. Zvaifler and L. B. Epstein,Analysis of the defects responsible for the impaired regulation of Epstein-Barr virus-induced B cell proliferation by rheumatoid arthritis lymphocytes. I. Diminished gamma interferon production in response to autologous stimulation. J. Exp. Med.157, 173–188 (1983).
S. C. Gilman, R. P. Carlson and A. J. Lewis,The immunological activity of Wy-18,251 (3-(p-chlorophenyl)thiazolo[3,2-a] benzimidazole-2-aretic acid). J. Immunopharmacol.7, 79–98 (1985).
R. L. Fenichel, H. E. Auburn, P. A. Schreck, R. Bloom and F. J. Gregory,Immunomodulating and antimetastatic activity of 3-(p-chlorophenyl)thiazole[3,2-a]benzimidazole-2-acetic acid) (Wy-18,251, NSC 310633). J. Immunopharmacol.2, 491–508 (1980).
S. C. Gilman, R. P. Carlson, J. Chang and A. J. Lewis,The antiinflammatory activity of the immunomodulator Wy-18,251 (3-(p-chlorphenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid). Agents and Actions17, 53–59 (1984).
S. C. Gilman, R. P. Carlson, J. F. Daniels, L. Datko, P. R. Berner, J. Chang and A. J. Lewis,Immunological abnormalities in rats with adjuvant-induced arthritis. II. Effect of antiarthritic therapy on immune function in relation to disease development. Int. J. Immunopharmacol. (1987) in press.
F. Hasler, H. G. Bluestein, N. J. Zvaifler and L. B. Epstein,Analysis of the defects responsible for the impaired regulation of EBV-induced B cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin E. J. Immunol.131, 768–772 (1983).
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Gilman, S.C., Bluestein, H.G. 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. Agents and Actions 21, 266–268 (1987). https://doi.org/10.1007/BF01966486
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DOI: https://doi.org/10.1007/BF01966486