IL‐6 receptor blockage inhibits the onset of autoimmune kidney disease in NZB/W F1 mice

In the present study, we examined the preventive effect of anti‐mouse IL‐6 receptor (IL‐6R) antibody, MR16‐1, on the development of autoimmune kidney disease in female NZB/W F1 (BWF1) mice. Immunological tolerance to MR16‐1 or isotype‐matched control antibody, KH‐5, was induced by the simultaneous administration of anti‐CD4 MoAb in mice. Thereafter, mice were intraperitoneally given 0.5 mg of MR16‐1, 0.5 mg of KH‐5 or saline once a week from 13 to 64 weeks of age. MR16‐1 treatment dramatically suppressed proteinuria and prolonged the survival time of BWF1 mice. Only one out of 10 mice died with high levels of proteinuria throughout the experiment. MR16‐1 almost completely suppressed the production of IgG forms of anti‐DNA and anti‐TNP antibodies, but not the IgM forms of these antibodies. In particular, all IgG subclasses (IgG1, IgG2a, IgG2b and IgG3) of anti‐DNA antibody production were significantly suppressed. Moreover, serum IgG1, IgG2a and IgG3 levels in MR16‐1‐treated mice were lower than those in saline‐ and KH‐5‐treated mice, whereas serum IgM and IgA levels were not influenced. In conclusion, MR16‐1 potently suppressed the development of autoimmune disease in BWF1 mice, and this was attributed to its effect of specific suppression of IgG class antibody production.