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Autoimmune kidney disease in MRL/Mp-lpr/lpr mice inhibited by OK-432, a streptococcal preparation
1Section of Immunopharmacology, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Company, Shizuoka, Japan.
Abstract:
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.
Insights
The anti-cancer drug OK-432, a tumor necrosis factor inducer, prevented autoimmune kidney disease in MRL/l mice. This immunostimulant therapy also extended lifespan, suggesting potential for treating human autoimmune conditions.
Area of Science:
- Immunology
- Pharmacology
- Nephrology
Background:
- Autoimmune diseases like lupus nephritis pose significant health challenges.
- MRL/Mp-lpr/lpr (MRL/l) mice are a model for studying autoimmune conditions.
- Immune complex-mediated glomerulonephritis is a hallmark of lupus nephritis.
Purpose of the Study:
- To investigate the efficacy of OK-432 in preventing autoimmune disease in MRL/l mice.
- To evaluate the impact of OK-432 on glomerulonephritis, survival, and autoantibody production.
- To determine the dose-dependent effects of OK-432 on autoimmune markers.
Main Methods:
- MRL/l mice were treated with varying doses of OK-432 starting at 8 weeks of age.
- Proteinuria and survival rates were monitored throughout the study.
- Immune complex deposition in glomeruli and autoantibody levels (IgM, IgG) were assessed.
- Lymphadenopathy and splenomegaly were evaluated.
Main Results:
- OK-432 treatment dose-dependently prevented glomerulonephritis and proteinuria.
- Survival time was significantly prolonged in OK-432 treated mice compared to controls.
- Immune complex deposition in glomeruli was reduced by OK-432.
- Serum IgM autoantibody levels increased, while IgG levels remained unchanged.
Conclusions:
- OK-432 demonstrates therapeutic potential in preventing and managing autoimmune kidney disease.
- The drug's ability to prolong survival highlights its protective effects.
- Further research into OK-432 for human autoimmune disease treatment is warranted.