ESTROGEN DECREASES IN-VITRO APOPTOSIS OF PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM WOMEN WITH NORMAL MENSTRUAL CYCLES AND DECREASES TNF-ALPHAPRODUCTION IN SLE BUT NOT IN NORMAL CULTURES

Estrogen has been suspected of causing changes in the lupus disease pr ocess by an as yet undetermined mechanism. In vitro apoptosis of perip heral blood mononuclear cells (PBMCs) in short-term unstimulated cultu res of systemic lupus erythematosus (SLE) cells is accelerated compare d to that in cells from normal individuals. To determine whether estro gen might be involved in regulating the rate of apoptosis in lupus, PB MCs or T cells from women with or without normal menstrual cycles were cultured for 16-20 hr with or without 30 ng/ml estradiol, The rate of apoptosis of the cells was measured, and supernatants of these cultur es were tested for various cytokines known tea affect apoptosis direct ly or indirectly, Compared to untreated cultures, estrogen significant ly reduced in vitro apoptosis of both patient (P < 0.05, n = 12) and n ormal (P < 0.001, n = 14) PBMCs if the donors had normal menstrual cyc les. Estrogen did not decrease apoptosis of noncycling patient (n = 8) nor of normal (n = 11) cells. Apoptosis of T cells cultured alone was not affected by estrogen. Supernatants from patients' estrogen-treate d PBMCs had significantly less TNF-alpha than untreated cultures (P < 0.05, n = 12). TNF-alpha levels from normals) cell cultures were uncha nged. Changes in hormone status (hysterectomy or menopause) alter estr ogen-sensitive apoptosis, which may be mediated through monocytes. Est rogen-induced decreases in apoptosis combined with decreased TNF-alpha production in the presence of estrogen may allow survival of autoimmu ne cells in SLE patients. (C) 1997 Academic Press.