Therapeutic studies in new zealand mice

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 F 1 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.