The beneficial effect of the estrogen antagonist, tamoxifen, on experimental systemic lupus erythematosus.

Abstract

To determine the effects of the estrogen antagonist, tamoxifen, on the development and the course of experimental murine systemic lupus erythematosus (SLE). SLE was induced in naive BALB/c female mice by injection of the human monoclonal anti-DNA antibody bearing the 16/6 idiotype (Id). Six weeks following immunization, when high levels of autoantibodies were demonstrated, the mice were treated with tamoxifen (200-800 micrograms/mouse twice a week) up to a period of 8 months. In several mouse groups tamoxifen treatment was started as late as one year following the immunization with the 16/6 Id when overt disease was already observed. Tamoxifen treatment had no effect on the 16/6 Id induced autoantibody production. However, the 16/6 Id immunized and tamoxifen treated mice demonstrated normal numbers of white blood cells (WBC) and thrombocytes while the untreated groups had significant leukopenia and thrombocytopenia. Similarly, persistent proteinuria and immune complex deposits in the kidneys were observed in the 16/6 Id immunized mice whereas no such deposits were found in kidney sections of 16/6 Id immunized mice that were treated with tamoxifen. Delayed tamoxifen treatment (starting a year following the immunization) also demonstrated beneficial therapeutic effects. These studies demonstrate therapeutic effects of tamoxifen on murine experimental SLE suggesting a possible role for this estrogen antagonist in the treatment of human SLE and related disorders.