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Cytokine‐induced Production of IL‐6 by Freshly Explanted Human Endometrial Stromal Cells

In exploring the link between the endocrine and the immune systems, we studied the modulation of secretion of IL-6 by estrogen in cytokine-induced freshly explanted human endometrial stromal cells. Stromal cells produced IL-6 in response to recombinant interleukin-1 (rIL-1) a or p, tumor necrosis factor, and interferon-gamma. This secretion was strongly inhibited by estradiol-17p at concentrations as low as M. Stromal cell IL-6 proteins in the size range of 23-30 kDa were detected by immunoprecipitation or immunoblotting procedures. The stromal cell IL-6 species were phosphorylated and differentially glycosylated in a manner comparable to the IL-6 secreted by the induced human peripheral blood monocytes and fibroblasts.' However, in contrast to the induction of IL-6 secretion in peripheral blood monocytes and fibroblasts, lipopolysaccharide did not induce the release of IL-6 into the culture medium of stromal cells. The IL-6-induced biological activity in the culture medium of the endometrial stromal cells was assayed by its enhancement of the al-antichymotrypsin secretion by Hep3B2 cells and the neutralization of this activity by anti-rIL-6 antiserum. Whereas the culture medium of the noninduced stromal cells did not exhibit biological activity beyond that seen in the untreated Hep3B2 controls, significant IL-6 biological activity was seen in the culture medium of IL-I-induced stromal cells. The IL-6induced biological activity of the culture medium of the IL-1-induced stromal cells was significantly higher than that seen in the culture medium of stromal cells that were pretreated with estradioLl7D M) and then induced with IL-1. These