Physiological concentration of estradiol inhibits polymorphonuclear leukocyte chemotaxis via a receptor mediated system.

Estrogen exhibits a variety of actions, including immuno-modulatory effects, in vivo and in vitro. The mechanism by which estrogen exerts its anti-inflammatory effect is not yet understood. We investigated the possible mechanisms of estradiol acting via the polymorphonuclear leukocytes (PMNs), which are important in the immune response. The agent, 17 beta-estradiol, but not 17 alpha-estradiol, significantly reduced PMNs chemotaxis to FMLP in a dose-dependent manner (control vs estrogen 10(-10)-(-6) M, P < 0.05). Physiological concentrations of estradiol significantly reduced the chemotaxis of PMNs (10(-10) mol). Pre-incubation with clomiphene or tamoxifen which are estrogen receptor antagonists, eliminated the inhibitory effect of 17 beta-estradiol on the chemotaxis of PMNs, restoring it to the control level. These observations suggest that 17 beta-estradiol suppressed the chemotaxis of PMNs by a receptor-dependent mechanism. In addition, the level of estradiol in human plasma, which PMNs were drawn, showed a close, inverse correlation with the PMNs chemotaxis to FMLP (r = -0.821 p < 0.001). Estrogen may modify the activity of neutrophils during the normal menstrual cycle, not only during pregnancy, and influence inflammation.