Adrenal and gonadal steroids inhibit IL-6 secretion by human marrow cells

Adrenal and gonadal steroids have protective effects on the skeleton that may be conferred partly by their ability to inhibit bone resorptive cytokines such as interleukin 6 (IL-6). We tested the hypothesis that IL-6 secretion by human marrow cells and a line of marrow stromal cells (KM101) is inhibited by dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT) and 17beta-oestradiol (E(2)). We also examined whether the estrogen status of the donor influenced the steroids' effects on IL-6 secretion. Femoral bone marrow was obtained from 19 postmenopausal women undergoing hip arthroplasty, and from seven subjects receiving oestrogen replacement therapy (ERT) at the time of surgery. Low-density mononuclear cells were isolated and cultured in IL-1beta-supplemented media, with or without DHEA, DHT or E(2). DHEA suppressed IL-6 more consistently than DHT or E(2): DHEA significantly suppressed IL-6 in 84% of cultures, DHT suppressed IL-6 in 58%, and E(2)did so in 50%. The magnitude of IL-6 inhibition was also greater for DHEA (group mean, treated/control of 62%) compared to DHT (81%) and E(2)(76%). In cultures from subjects receiving ERT, DHEA and DHT suppressed IL-6 in some, whereas E(2)did not suppress IL-6 secretion. Each steroid also significantly inhibited IL-6 secretion by KM101 cells. In summary, in marrow cultured from postmenopausal women, DHEA suppressed IL-6 secretion more consistently and to a greater degree than did DHT and E(2). Second, the inhibitory effect of E(2)was abrogated in marrow from women receiving ERT.