Abstract
The effect of leflunomide (HWA 486) was tested in proteoglycan-induced arthritis in an autoimmune animal model showing many similarities to human rheumatoid arthritis and ankylosing spondylitis. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immunity to host mouse cartilage proteoglycan. Arthritic and control (non-arthritic) animals were treated with 35 mg leflunomide/kg body weight/day for 12 weeks to suppress inflammatory events and antibody titers. Leflunomide suppressed acute inflammatory events, protected animals from new inflammatory episodes and acute exacerbations, slightly reduced the stiffness in joints and blocked the degradation of cartilage. The suppressive effect of leflunomide in proteoglycan-induced arthritis is due primarily to the suppression of autoantibody formation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
T. T. Glant, K. Mikecz, A. Arzoumanian and A. R. Poole,Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arth. Rheum.30, 201–212 (1987).
K. Mikecz, T. T. Glant and A. R. Poole,Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arth. Rheum.30, 306–318 (1987).
K. Mikecz, T. T. Glant, E. Buźas and A. R. Poole,Cartilage proteoglycans as potential autoantigens in humans and in experimental animals. Agents and Actions23, 63–66 (1988).
T. T. Glant, K. Mikecz, R. R. Bartlett, F. Deák, E. J.-M. A. Thornar, J. M. Williams, T. Mattar, K. E. Kuettner and R Schleyerbach,Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomide. Immunopharmacology23, 105–116 (1992).
J. M. Williams, J. Zurawski, K. Mikecz and T. T. Glant,Functional assessment of joint use in experimental inflammatory murine arthritis. J. Orthop. Res.11, 172–180 (1993).
E. Dayer, L. Mathai, T. T. Glant, K. Mikecz and A. R. Poole,Cartilage proteoglycan-induced arthritis in Balb/c: Antibodies recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis. Arth. Rheum.33, 1394–1405 (1990).
T. T. Glant, F. Fülöp, K. Mikecz, E. Buzás, G. Molnár and P. Erhardt,Proteoglycan-specific autoreactive antibodies and T-lymphocytes in experimental arthritis and human rheumatoid joint diseases. Biochem. Soc. Trans.18, 796–799 (1990).
K. Mikecz, T. T. Glant, E. Buzás and A. R. Poole,Proteoglycan-induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice. Arth. Rheum.33, 866–876 (1990).
K. Mikecz, and T. T. Glant,Migration and homing of lymphocytes to lymphoid and synovial tissues in proteoglycan-induced murine arthritis. Arth. Rheum.37, in press (1993).
R. R. Bartlett,Immunopharmacological profile of HWA 486, a noeel isoxazol derivative — II. In vivo immunomodulating effects differ from those of cyclophosphamide, prednisolone, or cyclosporin A. Int. J. Immunopharmacol.8, 199–204 (1986).
R. R. Bartlett and R. Schleyerbach,Immunopharmacological profile of a novel isoxazol derivative, HWA 486, with potential antirheumatic activity — I. Disease modifying action on adjuvant arthritis of the rat. Int. J. Immunopharmacol.7, 7–17 (1985).
R. R. Bartlett, S. Popovic and R. X. Raiss,Development of autoimmunity in MRL/lpr mice and the effects of drugs on this murine disease. Scand. J. Rheumatol.75, 290–299 (1988).
E. I. Buzás, K. Holló, L. Rubliczky, M. Garzó, P. Nyirkos and T. T. Glant,Effect of pregnancy on proteoglycan-induced progressive polyarthritis in Balb/c mice: Remission of disease activity. Clin. Exp. Immunol.94, 252–260 (1993).
T. T. Glant, K. Mikecz, E. Buzás, E. Dayer and A. R. Poole,Anti-proteoglycan antibodies in experimental spondylitis. In:Monoclonal Antibodies, Cytokines, and Arthritis, Mediators of Inflammation and Therapy, (Ed. T. Kresina) pp. 341–356, Marcel Dekker, New York 1991.
R. R. Bartlett, M. Dimitrijevic, T. Mattar, T. Zielinski, T. German, E. Rüde, G. H. Thoenes, C. C. A. Küchle, H.-U. Schorlemmer, E. Bremer, A. Finnegar and R. Schleyerbach,Leflunomide (HWA 486), a novel immuno-modulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection. Agents and Actions32, 10–21 (1991).
J. W. Williams, F. Xiao, P. F. Foster, A. Chong, S. Sharma, R. Bartlett and H. S. Sankary,Immunosuppressive effects of leflunomide in a cardiac allograft model. Transplant. Proc.25, 745–746 (1993).
A. S.-F. Chong, H. Gebel, A. Finnegan, E. E. Petraitis, X. L. Jian, H. N. Sankary, P. Foster and J. W. E. Williams,Leflunomide, a novel immunomodulatory agent: In vitro analyses of the mechanism of immunosuppression. Transplant. Proc.25, 747–749 (1993).
A. S.-F. Chong, A. Finnegan, X. Jiang, H. Gebel, H. N. Sankary, P. Foster and J. W. Williams,Leflunomide, a novel immunosuppressive agent: the mechanism of inhibition of T cell proliferation. Transplant. Proc.55, 1361–1366 (1993).
R. R. Bartlett, T. Mattar, U. Weithmann, H. Anagnostopulos, S. Popovic and R. Schleyerbach,Leflunomide, (HWA 486). A novel immunorestoring drug. In:Therapeutic Approaches to Inflammatory Diseases. (Eds. A. J. Lewis, N. S. Doherty and N. R. Ackerman) pp. 215–228, Elsevier, New York 1989.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Glant, T.T., Mikecz, K., Brennan, F. et al. Suppression of autoimmune responses and inflammatory events by leflunomide in an animal model for rheumatoid arthritis. Agents and Actions 41 (Suppl 2), C267–C270 (1994). https://doi.org/10.1007/BF01987665
Issue Date:
DOI: https://doi.org/10.1007/BF01987665