17-beta-estradiol suppresses IL-2 and IL-2 receptor

Interleukin-2 (IL-2) plays an important role in adaptive immune responses. These responses differ between females and males and may be due to the sex steroid estrogen. In this investigation we show that estrogen suppresses IL -2 production from activated peripheral blood T cells and CD4+ T cell lines at the transcriptional level. Suppression of IL-2 occurred at short term, high 17-beta -estradiol concentrations as well as longer term lower 17-beta -estradiol concentrations. In CD4+ Jurkat T cells, suppression of IL-2 was associated with decreased nuclear binding of two important IL-2 promoter t ranscription factors: NF kappaB and AP-1. The decreased nuclear binding of NF kappaB occurred in the setting of estrogen-induced increases in I kappaB alpha protein levels, an important inhibitor of NF kappaB nuclear transloc ation. 17-beta -Estradiol was also shown to inhibit IL-2 receptor (IL-2R) e xpression in activated peripheral blood T cells. Estrogen-induced suppressi on of IL-2 and its receptor may have many ramifications for our understandi ng of immune and autoimmune sexual dichotomies, immune responses during pre gnancy, and potential therapeutic intervention with hormone agonists and an tagonists. (C) 2001 Academic Press.