THE BENEFICIAL EFFECT OF THE ESTROGEN ANTAGONIST, TAMOXIFEN, ON EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. To determine the effects of the estrogen antagonist, tamoxi fen, on the development and the course of experimental murine systemic lupus erythematosus (SLE). Methods. SLE was induced in naive BALB/c f emale mice by injection of the human monoclonal anti-DNA antibody bear ing the 16/6 idiotype (Id). Six weeks following immunization, when hig h levels of autoantibodies were demonstrated, the mice were treated wi th tamoxifen (200-800 mu g/mouse twice a week) up to a period of 8 mon ths. In several mouse groups tamoxifen treatment was started as late a s one year following the immunization with the 16/6 Id when overt dise ase was already observed. Results. Tamoxifen treatment had no effect o n the 16/6 Id induced autoantibody production. However, the 16/6 Id im munized and tamoxifen treated mice demonstrated normal numbers of whit e blood cells (WBC) and thrombocytes while the untreated groups had si gnificant leukopenia and thrombocytopenia. Similarly, persistent prote inuria 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. D elayed tamoxifen treatment (starting a year following the immunization ) also demonstrated beneficial therapeutic effects. Conclusion. These studies demonstrate therapeutic effects of tamoxifen on murine experim ental SLE suggesting a possible role for this estrogen antagonist in t he treatment of human SLE and related disorders.