Therapeutic effects of TACI-Ig on rats with adjuvant-induced arthritis via regulating T cell-mediate

来源 :中国药理学会第十一次全国学术会议 | 被引量 : 0次 | 上传用户:benbenwenwen
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  OBJECTIVE To investigate the effects of TACI-Ig, a recombinant fusion protein that modulates B and T cells activation by binding and neutralizing B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), on established adjuvant arthritis (AA) rat model.METHODS The rats with experimental arthritis were randomly separated into different groups and then treated with TACI-Ig (0.7, 2.1, 6.3 mg·kg-1, sc), rhTNFR-Fc (2.8 mg·kg-1, sc), methotrexate (MTX) (0.5 mg·kg-1,ig) or IgG-Fc (6.3 mg·kg-1 , sc) respectively once per day from day 16 to 34 after immunization.Arthritis was evaluated by hind paw swelling, polyarthritis index, histopathological examination.Activities of BLyS, APRIL, interleukin (IL)-1 β, IL-2, IL-10, transforming growth factor-β1 (TGF-β1), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interferon (IFN)-γ, immunoglobulin (Ig) G1, IgG2a, IgM, and IgA were assessed by enzyme linked immunosorbent assay (ELISA).The expression of CD3, CD20, CD68, and BLyS were detected by immunostaining analysis.T cell populations are analysed by flow cytometric analysis.RESULTS TACI-Ig (2.1,6.3 mg· kg-1) treatment significantly reduced the severity of established arthritis using the methods of clinical observation and histopathological examination.TACI-Ig treatment inhibited expression of IgM, decreased the expression of BLyS and APRIL and regulated the balance of pro-inflammatory and anti-inflammatory cytokines in serum of AA rats.Subcutaneous administration of TACI-Ig significantly suppressed the levels of BLyS and APRIL in ST of AA rats.The expression of CD3, CD20, and BLyS in ST and the expression of CD3, CD68, and BLyS in spleen were decreased after treatment with TACI-Ig.TACI-Ig enhanced the decreased total and activated CD4 + T cell in peripheral blood lymphocytes and spleen cells of rats in AA.CONCLUSIUON Administration of TACI-Ig significantly attenuates progression of experimental arthritis, with reductions in inflammatory response and bone and joint destruction.Local production of BLyS and APRIL may foster survival and/or expansion of B cells that produce pathogenic autoantibodies and/or promote local T cell activation and consequent joint destruction.TACI-Ig therefore represents a potentially new immunotherapeutic agent for the management of arthritis as well as other autoimmune diseases that involve both B and T cells.
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