Therapeutic studies in NZB/W MICE

Steinberg, Alfred D.; Gelfand, Michael; Hardin, John A.; Löwenthal, David

doi:10.1002/art.1780180102

Cited by 85 publications

(8 citation statements)

References 12 publications

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“…Direct PFC assays were carried out after 5 days of culture ( Autoantibodies in Chimeric Mice. BXSB male mice regularly showed high titers of ANA and anti-dsDNA antibodies, whereas CBA and B6 mice lacked these antibodies (Table 3 lymphoid irradiation (13), whole-body irradiation (14), radiomimetric cytotoxic drug therapy (27,28), and antilymphocyte or anti-@ treatments have been used with some success (29,30). Most efforts to apply marrow transplantation have employed marrow from H-2-matched donors or congeneic donors that permit introduction of cells bearing only a few genes from autoimmune-resistant donors that differ from the genes of the recipients.…”

Section: Methodsmentioning

confidence: 99%

Marrow transplantation from tolerant donors to treat and prevent autoimmune diseases in BXSB mice.

Himeno

Good²

1988

Proc. Natl. Acad. Sci. U.S.A.

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Section: Methodsmentioning

confidence: 99%

Marrow transplantation from tolerant donors to treat and prevent autoimmune diseases in BXSB mice.

Himeno

Good²

1988

Proc. Natl. Acad. Sci. U.S.A.

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“…This was especially disappointing in view of its efficacy in hereditary angioedema in humans (27) and its relative freedom from masculinizing side effects. However, we found that mice as old as 8 months of age, which as a group have failed to respond to immunosuppressive therapy (28), responded to testosterone treatment with significant prolongation of survival. Thus, it is possible that sex hormones provide a therapeutic modality different from other forms of therapy.…”

Section: Discussionmentioning

confidence: 80%

Therapeutic studies in new zealand mice

Melez

Boegel

Steinberg

1980

Arthritis & Rheumatism

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In view of the known inhibitory effects of androgens on the spontaneous production of autoantibodies in hybrids of NZB mice, as well as the dramatic effects of sex hormones on the modulation of autoimmunity in NZB/NZW F1 mice, we undertook a systematic study of treatment of female NZB/NZW mice with androgens. We initiated treatment at 0.5, 3, 5, 6, 7, or 8 months of life in castrated or intact mice by use of one of three steroid preparations at different doses. We found that danazol was not effective in suppressing proteinuria, reducing antibodies to ssDNA, or in prolonging survival. In contrast, both testosterone and 5 α‐dihydrotestosterone were capable of prolonging survival, suppressing proteinuria, and reducing anti‐ssDNA in both intact and castrated mice. Testosterone was effective at lower doses than was the 5 α hormone. Testosterone significantly prolonged survival even when started after the onset of clinical illness at 5, 7, and 8 months of age. Mice treated from 5 months of life with testosterone had a much more marked reduction in antibodies to ssDNA than to native DNA. However, treatment from 7 months of age significantly prolonged survival without altering the serum levels of either autoantibody, suggesting that some other mechanism of testosterone action may be contributing to therapeutic efficacy. These studies indicate that androgen therapy may be beneficial even after the development of clinical illness, that castration is not necessary for benefit, and that the effectiveness of a therapeutic regimen is dependent upon both the dose and the particular preparation of hormone.

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“…There is general agreement, parallel with studies of the animal analogue, the NZB/NZW Fi hybrids, that established severe renal dis ease is refractory to steroid therapy [12], Al ternative forms of immunosuppressive therapy have therefore been tried. A critical evaluation of the results of treatment with azathioprine and cyclophosphamide suggests that the effi cacy of neither agent is proven in the manage ment of patients with lupus nephritis [6], Pre liminary data regarding the use of chloram bucil and nitrogen mustard appear more pro mising [13,14], and both drugs merit further controlled trials as alternative or adjunctive modes of therapy.…”

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confidence: 82%