Anti‐interleukin‐6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus

<jats:title>Summary</jats:title><jats:p>Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from dysregulation of the immune system. Interleukin‐6 (IL‐6) is a multifunctional cytokine produced by macrophages, monocytes and T and B cells. It stimulates B‐cell differentiation/maturation, immunoglobulin secretion, and T‐cell functions. Elevated levels of IL‐6 in serum, urine and renal glomeruli were detected in patients with active SLE and in murine models of SLE. Our study investigated the role of IL‐6 in an SLE‐like disease in New Zealand Black/White (NZB/W) F<jats:sub>1</jats:sub> mice by administration of an anti‐murine IL‐6 monoclonal antibody (mAb). Intraperitoneal administration of the anti‐IL‐6 mAb suppressed the production of anti‐dsDNA autoantibody. B‐cell proliferation induced by anti‐IgM and anti‐CD40 was lower in the anti‐IL‐6 mAb‐treated mice, <jats:italic>ex vivo</jats:italic> studies demonstrated that anti‐IL‐6 mAb treatment inhibited anti‐dsDNA production. Anti‐CD3‐induced T‐cell proliferation and mixed lymphocyte reactions were inhibited by anti‐IL‐6 mAb treatment, indicating a partial down‐regulation of T cells. Histological analysis showed that treatment with anti‐IL‐6 mAb prevented the development of severe kidney disease. These results suggest that treatment with anti‐IL‐6 mAb has a beneficial effect on autoimmunity in murine SLE and that autoreactive B cells may be the primary target for anti‐IL‐6 mAb treatment; its effect on autoreactive T cells is also indicated.</jats:p>