An immunomodulating anti-rheumatic drug, lobenzarit disodium (CCA): inhibition of polyclonal B-cell activation and prevention of autoimmune disease in MRL/Mp-lpr/lpr mice.
In this study, we examined the effect of an immunoregulatory antirheumatic agent, lobenzarit disodium (CCA), on spontaneously developing glomerulonephritis in MRL/Mp-lpr/lpr (MRL/l) mice. Starting from 6 weeks of age, mice were given CCA orally 5 days a week at a dose of 2 or 10 mg/kg. A control group was given the same volume of distilled water. The CCA treatment suppressed the excretion of protein in the urine. At 40 weeks of age, the incidence of proteinuria was 10/10 in the controls, 6/10 in the 2-mg/kg treatment group, and 5/10 in the 10 mg/kg group. The life span was prolonged dose dependently. The 50% survival time was 33 weeks for the controls, 35.5 weeks for the 2-mg/kg group, and 41 weeks for the 10-mg/kg group. The serum levels of anti-ssDNA antibody, anti-TNP antibody, and rheumatoid factor (RF) of the Ig G isotype and immune complex were reduced compared with control group. But the antibodies of Ig M isotype were not reduced. The serum Ig G1, Ig G2, and Ig G3 were significantly lower in the CCA-treated mice than in the controls. But again the serum level of Ig M was unchanged. These effects of CCA may be based on the suppression of lymphadenopathy. CCA may correct abnormal B-cell growth and differentiation factor release by the MRL/l abnormal T cells. These results show that CCA inhibits the development of lupus nephritis in MRL/l mice through the amelioration of the abnormal immune response, polyclonal B-cell activation.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D000936:Antigen-Antibody Complex / Q000032:analysis; D001327:Autoimmune Diseases / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis; D008136:Longevity / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008221:Lymphoid Tissue / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011507:Proteinuria / Q000235:genetics; D012217:Rheumatoid Factor / Q000032:analysis; D014301:Trinitrobenzenes / Q000276:immunology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D004277:DNA, Single-Stranded; D007136:Immunoglobulins; D014301:Trinitrobenzenes; D062367:ortho-Aminobenzoates; D012217:Rheumatoid Factor; C015735:lobenzarit