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  • Title: Animal models utilized in the research of autoimmune disease control: experimental therapy of glomerulonephritis in NZB/W F1 mice.
    Author: Okudaira H, Terada E, Okudaira K.
    Journal: Prog Clin Biol Res; 1987; 229():157-74. PubMed ID: 3601985.
    Abstract:
    Treatment of 8-month-old NZB/W F1 mice with Cyclosporin A (CsA) significantly depressed the increase in blood urea nitrogen (BUN) levels and clearly prolonged the life span. Concentrations of anti-DNA antibodies and circulating immune complexes in the serum were not affected. Deposition of IgG and C3 was remarkably decreased by administration of CsA. Histological examination indicated that glomerulonephritis in CsA treated NZB/W F1 mice was much milder than that in untreated control animals. Seven-month-old NZB/W F1 mice were inoculated with 5 X 10(7) NZW spleen cells. The mice so treated showed a clear fall of anti-double-stranded (ds) DNA antibody titers accompanied by a decrease in BUN concentration. Mice so treated showed markedly increased survival times (more than 17 months) compared with untreated controls (mean +/- SD 8.38 +/- 0.75 months). A cell fractionation study suggested that T cells among NZW spleen cells play a major role. Recipients of the unfractionated or the T-cell fraction of NZW spleen cells had histologically less glomerulonephritis than untreated control NZB/W F1 mice. NZW B-cell transfer to NZB/W F1 mice had no effect. Serum obtained from NZB/W F1 mice receiving NZB/W spleen cells 10 days previously [graft-vs-host reaction (GVHR) serum] was injected into 8-month-old NZB/W F1 mice. A clear fall in anti-ds DNA antibody titers and inhibition of age-associated sharp increases in BUN were observed. The mean life span of these mice (10.50 +/- 0.58 months) was significantly longer than that of untreated controls (8.69 +/- 0.38 months). GVHR serum had the ability to suppress anti-ds DNA antibody formation by NZB/W F1 spleen cells in vitro. Allogeneic GVHR serum prepared in C57B1/6 X DBA/2 (B6D2F1) mice by transferring C57B1/6 spleen cells was also effective in suppressing anti-ds DNA antibody formation in vitro.
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