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.
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.
Mihara
M
M
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Ohsugi
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001688:Biological Products / Q000494:pharmacology*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000097:blood / Q000401:mortality / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008814:Mice, Inbred NZB; D010844:Picibanil / Q000494:pharmacology*; D011507:Proteinuria / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology* / Q000502:physiology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D001688:Biological Products; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil; D004247:DNA; D002784:Cholesterol