THE BENEFICIAL-EFFECTS OF TREATMENT WITH TAMOXIFEN AND ANTI-ESTRADIOLANTIBODY ON EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS ARE ASSOCIATED WITH CYTOKINE MODULATIONS

In an attempt to elucidate the role of oestrogens in systemic lupus er ythematosus (SLE) we investigated the effects of treatment with an oes trogen antagonist - tamoxifen and a monoclonal anti-oestradiol (anti-E 2) antibody on mice in which experimental systemic lupus erythematosus (SLE) was induced by a human monoclonal anti-DNA antibody bearing the 16/6 idiotype (16/6 Id). Thus, groups of BALB/c female mice were immu nized with the 16/6 Id and 3 weeks following the booster injection, wh en antibody titres were elevated in the injected mice, treatment proto cols with anti-oestradiol or tamoxifen were initiated. Control groups that were not immunized with the 16/6 Id but were similarly treated wi th the above agents were included in the study. The treatment with the above agents had no effect on the total autoantibody titres; however, a decrease in the immunoglobulin G (IgG)2a/IgG(1) ratio of the anti-D NA antibodies was determined in the 16/6 Id immunized and treated mice . Further, both the anti-oestradiol and tamoxifen had beneficial effec ts on the clinical manifestations (white blood cell counts, levels of protein in the urine and immune complex deposits in the kidneys) of th e 16/6 Id immunized and treated mice. We have previously observed a si gnificant elevation in interleukin-1 (IL-1) and tumour necrosis factor -alpha (TNF-alpha) secretion in mice with experimental SLE and a reduc tion in IL-2, IL-4 and interferon-gamma (INF-gamma) levels as compared with the levels detected in healthy controls. Treatment with either t he anti-oestradiol antibody or with tamoxifen restored the levels of a ll the above cytokines to the normal levels observed in the control mi ce. These findings suggest that cytokine modulation may be the basis f or the therapeutic effects of both anti-oestrogens in experimental SLE .