Androgenic hormones modulate autoantibody responses and improve survival in murine lupus.
Antibodies to native DNA and to polyadenylic acid (Poly A) occur spontaneously and undergo a regulated switch from IgM to IgG during the course of autoimmune disease in NZB/NZW F(1) (B/W) mice. B/W females have higher titers and earlier commitment to 7S antibodies to DNA and Poly A, whereas B/W males bind DNA and Poly A primarily by 19S antibodies. We have performed castration experiments to determine the effects of sex hormones on this switch from IgM to IgG.NZB/NZW F(1) (B/W) mice were either castrated or subjected to sham surgery at 2 wk of age and studied for immunoglobulin class of antibodies to nucleic acids at 4, 6, and 7 mo post-surgery. Prepubertal castration of males caused premature death in 60% of mice. Castrated males had a significant decline in their serum testosterone concentration, an increase in DNA and Poly A binding, and an accelerated switch from 19S to 7S antibodies to nucleic acids. Castrated females had no change in mortality. However, castrated females given maintained androgen treatment had a decreased mortality compared to castrated females receiving estrogen (14 vs. 94%). The anticipated switch to 7S antibodies to Poly A was almost eliminated in castrated females. These results suggest that sex hormones modulate immunologic regulation and that androgenic hormones are protective in murine lupus.
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D002369:Castration; D004247:DNA / Q000276:immunology; D004343:Drug Implants; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007109:Immunity; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000401:mortality; D008297:Male; D051379:Mice; D011061:Poly A / Q000276:immunology; D012737:Sex Factors; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D001323:Autoantibodies; D004343:Drug Implants; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011061:Poly A; D013739:Testosterone; D004247:DNA