Induction of high-dose tolerance to the rat anti-mouse IL-6 receptor antibody in NZB/NZW F1 mice.

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.