Oestradiol inhibits the release of tumour necrosis factor but not interleukin 6 from adult human osteoblasts in vitro

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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 17β-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 M17β-oestradiol, producing an average 30% reduction in TNF release. In contrast 17β-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 17β-oestradiol (10−9M) under stimulatory conditions. rhIL-lα (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.