Modulation of lymphokine-induced macrophage activation by estrogen metabolites.

Abstract

Pharmacological doses of estrogens such as 17-beta estradiol (17- beta E) and diethylstilbestrol (DES) activate macrophages in a thymic-dependent manner in vivo. In this report, we investigated the direct in vitro effects of 17- beta E and its major metabolites on macrophage activation in response to lectin-stimulated lymphocyte supernatants containing macrophage-activating factor (MAF), a T cell lymphokine (LK). Activation was measured in terms of macrophage cytostasis against cultured tumor cells. As suggested by previous studies with quinone metabolites of benzene, the catechol estrogen metabolite 2-OH estrone (2-OH E) was the most potent metabolite at suppressing LK-induced macrophage activation. However, if macrophages were first LK-induced, and then exposed to estrogens before addition of tumor cells, then all the estrogens, including 2-OH E, enhanced cytostasis. These observations suggested membrane-mediated immunomodulation of macrophage function by estrogen metabolites and, indirectly, a role for the thymus in these effects via the maintenance of a mature, LK-producing T cell population necessary for macrophage activation.