Natural history of murine lupus. Modulation by sex hormones

Pathologic and immunologic features of the spontaneous autoimmune disease of NZB and NZB/NZW F1 (B/W) mice resemble human SLE in three major respects: formation of antibodies to nucleic acids, deposition of immune complexes containing DNA in the kidney, and earlier onset of severe disease in females. Genetic, viral, and hormonal factors are involved in a pathogenetic mechanism that is manifest primarily as a disturbance in immunologic regulation. Recent studies on the sequential development of IgM and then IgG antibodies to DNA and RNA suggest that the thymus, spleen, and gonads exert important regulatory influences. We have found that sex hormones modulate the expression of autoimmunity in B/W mice, with androgens suppressing and estrogens accelerating disease. The hormones may act by restoring immunologic control.