The biological response modifier OK-432 (a streptococcal preparation) inhibits the development of autoimmune kidney disease in NZB/W F1 hybrid mice: possible involvement of tumor necrosis factor

Abstract

OK-432 (a streptococcal preparation) has been widely used for cancer immunotherapy in Japan. It is a potent immunostimulator, activating macrophages and T lymphocytes, and increasing the production of TNF and several other cytokines in both humans and animals. In the present study, we evaluated the prophylactic effect of OK-432 on the development of autoimmune kidney disease in NZB/W F1 (BWF1) mice. The mice were given 0.5 or 2.0 KE ('klinische Einheit'; clinical unit) of OK-432 intraperitoneally every week from 21 weeks of age to the time of death. The control group received the same volume of saline (vehicle). OK-432 delayed the development of proteinuria and prolonged the survival of these mice dose dependently. At 49 weeks, 33.3% of control mice were alive, whereas 55.6% in the 0.5-KE- and 75% in the 2.0-KE-treated mice were alive. In the control group, the serum cholesterol level increased due to the development of glomerulonephritis. In contrast, mice treated with OK-432 had significantly lower levels of serum cholesterol. The serum levels of anti-DNA and anti-TNP antibodies were not affected by OK-432 administration. OK-432 induced the production of tumor necrosis factor (TNF)-alpha in the peritoneal fluid in the BWF1 mice. These results indicate that the effect of OK-432 in preventing the development of autoimmune disease in the mice may result from the stimulation of the endogenous TNF-alpha production.