ESTRADIOL INHIBITS THE RELEASE OF TUMOR-NECROSIS-FACTOR BUT NOT INTERLEUKIN-6 FROM ADULT HUMAN OSTEOBLASTS INVITRO

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) M17-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.