title: Oestradiol inhibits the release of tumour necrosis factor but not interleukin 6 from adult human osteoblasts in vitro.
abstract: Oestrogens may control bone remodelling by directly regulating the synthesis of cytokines in osteoblasts. We have investigated the effects of oestradiol on the release of two cytokines, IL-6 and TNF, known to be produced by normal human osteoblast-like cells. The effect of oestradiol on basal and stimulated IL-6 and TNF release was investigated. The concentration of IL-6 and TNF in 24 h bone cell-conditioned medium was determined using bio- and immunoradiometric assays. The results showed that 17 beta-oestradiol (10(-10) and 10(-8) M) inhibited IL-1-stimulated TNF release in a dose dependent manner in 7 out of 9 patients. Maximal inhibition was observed with 10(-8) M 17 beta-oestradiol, producing an average 30% reduction in TNF release. In contrast 17 beta-oestradiol (10(-12)-10(-8) M) failed to consistently regulate basal or stimulated IL-6 release. IL-6 mRNA levels were also shown not to be modulated by 17 beta-oestradiol (10(-9) M) under stimulatory conditions. rhIL-1 alpha (10 U/ml) was a consistent and potent stimulator of IL-6 and TNF release, and the glucocorticoid hydrocortisone was found to be a powerful suppressor of both IL-6 and TNF release under basal or stimulatory conditions. In conclusion direct regulation of bone remodelling by oestradiol does not appear to be effected via the control of IL-6 production in osteoblasts. However, a suppression of osteoblastic TNF release could represent one facet of the control of bone formation and resorption by oestrogens.
authors.affiliation: Bath Institute for Rheumatic Diseases, UK.
authors.forename: D
authors.initials: D
authors.lastname: Rickard
authors.forename: G
authors.initials: G
authors.lastname: Russell
authors.forename: M
authors.initials: M
authors.lastname: Gowen
mesh_terms: D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol