ADRENAL AND GONADAL STEROIDS INHIBIT IL-6 SECRETION BY HUMAN MARROW CELLS

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2001-12, Vol.16 (5), p.178-186
• Main Authors: Gordon, C.M., LeBoff, M.S., Glowacki, J.
• Format: Article
• Language: English
• Subjects: Adrenal Glands - metabolism; Adult; Aged; Aged, 80 and over; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; bone resorption/dehydroepiandrosterone/oestrogen replacement therapy/interleukin 6; Cell Line; Cells, Cultured; Dehydroepiandrosterone - metabolism; Dehydroepiandrosterone - pharmacology; Dihydrotestosterone - metabolism; Dihydrotestosterone - pharmacology; Estradiol - metabolism; Estradiol - pharmacology; Estrogen Replacement Therapy; Estrogens - metabolism; Estrogens - pharmacology; Female; Humans; Interleukin-6 - secretion; Middle Aged; Ovary - metabolism; Postmenopause - metabolism; Postmenopause - physiology; Stromal Cells - cytology
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2001.0962

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 17β-oestradiol (E2). 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-1β-supplemented media, with or without DHEA, DHT or E2. DHEA suppressed IL-6 more consistently than DHT or E2: DHEA significantly suppressed IL-6 in 84% of cultures, DHT suppressed IL-6 in 58%, and E2did 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 E2(76%). In cultures from subjects receiving ERT, DHEA and DHT suppressed IL-6 in some, whereas E2did 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 E2. Second, the inhibitory effect of E2was abrogated in marrow from women receiving ERT.