Delayed androgen treatment prolongs survival in murine lupus.

Abstract

Female NZB/NZW F1 mice were treated as adults with 5-alpha-dihydrotestosterone powder packed into subcutaneous implants. Two treatment protocols were followed: (a) 3-mo-old mice received 6 mg of androgen, and (b) 6-mo-old mice were castrated and given 12 mg of androgen. Sham females received empty implants. Mice were followed monthly for surival, for antibodies to DNA and polyadenylic acid, and for renal histopathology. The percent survival at 11 mo was 74% for mice treated at 3 mo, compared to 11% for the sham controls, and 100% for mice treated at 6 mo, compared to 20% for their sham controls. Androgen-treated mice had less immune complex glomerulonephritis as determined by immunofluorescent and electron microscopy. Surprisingly, treated mice had no significant sustained reduction in antibodies to DNA although they had reduced antibodies to polyadenylic acid. These results suggest that androgens can still prolong survival and reduce immune complex deposition even when treatment is delayed to an age when disease is relatively established. After delayed androgen treatment, mice survive despite the presence of high levels of IgG antibodies to DNA.