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.
Mihara
M
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd, Shizuoka, Japan.
Takagi
N
N
Takeda
Y
Y
Ohsugi
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology*; D051379:Mice; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015850:Interleukin-6; D019947:Receptors, Interleukin-6