The beneficial effects of treatment with tamoxifen and anti-oestradiol antibody on experimental systemic lupus erythematosus are associated with cytokine modulations

In an attempt to elucidate the role of oestrogens in systemic lupus erythematosus (SLE) we investigated the effects of treatment with an oestrogen antagonist - tamoxifen and a monoclonal anti-oestradiol (anti-E2) 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 immunized with the 16/6 Id and 3 weeks following the booster injection, when antibody titres were elevated in the injected mice, treatment protocols with anti-oestradiol or tamoxifen were initiated. Control groups that were not immunized with the 16/6 Id but were similarly treated with 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-DNA antibodies was determined in the 16/6 Id immunized and treated mice. Further, both the anti-oestradiol and tamoxifen had beneficial effects on the clinical manifestations (white blood cell counts, levels of protein in the urine and immune complex deposits in the kidneys) of the 16/6 Id immunized and treated mice. We have previously observed a significant elevation in interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) secretion in mice with experimental SLE and a reduction in IL-2, IL-4 and interferon-gamma (INF-gamma) levels as compared with the levels detected in healthy controls. Treatment with either the anti-oestradiol antibody or with tamoxifen restored the levels of all the above cytokines to the normal levels observed in the control mice. These findings suggest that cytokine modulation may be the basis for the therapeutic effects of both anti-oestrogens in experimental SLE.