title: Induction of high-dose tolerance to the rat anti-mouse IL-6 receptor antibody in NZB/NZW F1 mice.
abstract: MR16-1 is a monoclonal antibody to mouse IL-6 receptor (IL-6R) and a good tool to investigate the involvement of IL-6 in mouse disease models. However, long-term administration of MR16-1 induced anti-MR16-1 antibody that inhibited IL-6 blocking activity of MR16-1. In this study, we treated NZB/NZW F1 (BWF1) mice with MR16-1 (0.5 mg, weekly) and tested for proteinuria (an indicator of autoimmune disease) after inducing tolerance by intraperitoneal injection of anti-CD4 mAb, or in an exploratory experiment, by prior intravenous injection of 2 mg MR16-1. Anti-CD4 mAb treatment inhibited anti-MR16-1 antibody production. And the appearance of proteinuria was significantly delayed. However, anti-CD4 mAb injection alone also significantly delayed the onset of nephritis compared with saline treatment. Intravenous MR16-1 (2 mg) followed by weekly MR16-1 injections inhibited the production of anti-MR16-1 antibody and consequently decreased the prevalence of proteinuria and the level of anti-DNA antibodies. These results established the viability of intravenous MR16-1 injection as a means of inducing tolerance. It is superior to the anti-CD4 mAb method because it enabled the effects of MR16-1 monotherapy to be evaluated without the confounding effects of anti-CD4 mAb.
authors.affiliation: Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135, Komakado, Gotemba, Shizuoka 412-8513, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Yoshida
authors.forename: Misato
authors.initials: M
authors.lastname: Hashizume
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mihara
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D015704:CD4 Antigens / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006579:Heterozygote; D007108:Immune Tolerance / Q000187:drug effects* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D008819:Mice, Nude; D011507:Proteinuria / Q000276:immunology / Q000517:prevention & control; D051381:Rats; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
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