Autoimmune kidney disease in MRL/Mp-lpr/lpr mice inhibited by OK-432, a streptococcal preparation.
Autoimmune MRL/Mp-lpr/lpr (MRL/l) mice were treated with the immunostimulating anti-cancer drug OK-432 (a streptococcal preparation), a potent inducer of tumour necrosis factor. Treatment was initiated at 8 weeks of age, before the onset of the autoimmune disease. OK-432 prevented the development of immune complex-mediated glomerulonephritis in a dose-dependent manner, and prolonged the life in this strain of mice. At 36 weeks of age, the incidence of proteinuria was 90% in the controls, 60% in the 0.5-KE(1 KE = 0.1 mg) treatment group, and 33% in the 2.0-KE group. The 50% survival time was 23 weeks for the controls; 32 weeks for the 0.5-KE group; and greater than 36 weeks for the 2.0-KE group. Immune complex deposition in glomeruli was significantly reduced in the treated groups. The IgM class of serum autoantibody levels was significantly increased by OK-432 treatment but the IgG class was almost unchanged. Furthermore, lymphadenopathy and splenomegaly were not suppressed. The results indicate that OK-432 may be useful in the treatment of autoimmune disease in humans.
Mihara
M
M
Section of Immunopharmacology, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Company, Shizuoka, Japan.
Ohsugi
Y
Y
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001688:Biological Products; D005260:Female; D008181:Lupus Nephritis / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010844:Picibanil / Q000627:therapeutic use*
D001323:Autoantibodies; D001688:Biological Products; D010844:Picibanil