title: Adrenal and gonadal steroids inhibit IL-6 secretion by human marrow cells.
abstract: 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.
authors.affiliation: Division of Adolescent/Young Adult Medicine, Children's Hospital, Boston, MA 02115, USA. catherine.gordon@tch.harvard.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Gordon
authors.forename: M S
authors.initials: MS
authors.lastname: LeBoff
authors.forename: J
authors.initials: J
authors.lastname: Glowacki
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000378:metabolism* / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008875:Middle Aged; D010053:Ovary / Q000378:metabolism; D017698:Postmenopause / Q000378:metabolism / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology
chemical_list: D004967:Estrogens; D015850:Interleukin-6; D013196:Dihydrotestosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol