Estrogen decreases in vitro apoptosis of peripheral blood mononuclear cells from women with normal menstrual cycles and decreases TNF-alpha production in SLE but not in normal cultures.

Estrogen has been suspected of causing changes in the lupus disease process by an as yet undetermined mechanism. In vitro apoptosis of peripheral blood mononuclear cells (PBMCs) in short-term unstimulated cultures of systemic lupus erythematosus (SLE) cells is accelerated compared to that in cells from normal individuals. To determine whether estrogen might be involved in regulating the rate of apoptosis in lupus, PBMCs 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 cultures were tested for various cytokines known to affect apoptosis directly or indirectly. Compared to untreated cultures, estrogen significantly reduced in vitro apoptosis of both patient (P < 0.05, n = 12) and normal (P < 0.001, n = 14) PBMCs if the donors had normal menstrual cycles. 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-treated PBMCs had significantly less TNF-alpha than untreated cultures (P < 0.05, n = 12). TNF-alpha levels from normals' cell cultures were unchanged. Changes in hormone status (hysterectomy or menopause) alter estrogen-sensitive apoptosis, which may be mediated through monocytes. Estrogen-induced decreases in apoptosis combined with decreased TNF-alpha production in the presence of estrogen may allow survival of auto-immune cells in SLE patients.