REGULATION OF INTERLEUKIN-6 EXPRESSION IN HUMAN OSTEOBLASTIC CELLS IN-VITRO

Interleukin-6 (IL-6) is a potent stimulator of bone resorption which h as been demonstrated in a variety of in vivo and in vitro models. We i nvestigated the regulation of IL-6 secretion in primary human osteobla stic cells (HOC) in vitro by cytokines known to play an important role in coupling bone formation to bone resorption. HOC were isolated from healthy adults who underwent selective orthopedic surgery and treated with cytokines released in the bone microenvironment during coupling i.e Interleukin-1 beta (IL-1 beta), Tumor Necrosis Factor alpha (TNF a lpha), Transforming Growth Factor beta 1 and 2 (TGF beta 1 and 2) and Endothelin-1 (ET-1). Furthermore, we determined whether systemically-a cting steroid hormones of gonadal and adrenal origin as well as glucoc orticoids affect the local regulation of IL-6 secretion in primary HOC . To examine the effects of different steroid hormones on IL-6 product ion, HOC were exposed to estradiol (E2), dihydrotestosterone (DHT), de hydroepiandrosterone (DHEA) and dexamethasone (Dexa) with and without a subsequent treatment of the HOC populations with cytokines. We obser ved that (1) IL-1 beta and TNF alpha induced IL-6 in a dose and time-d ependent fashion, (2) TGF beta 1 and 2 enhanced basal and IL-1 beta an d TNF alpha induced IL-6 expression, (3) ET-1 elicited a dose-dependen t stimulatory effect on IL-6 expression. (4) E2, DHT and DHEA alone an d in combination with IL-1 beta and TNF alpha elicited no reproducible dose-dependent effect on IL-6 production, whereas Dexa inhibited basa l and IL-1 beta and TNF alpha induced IL-6 expression dose dependently . In conclusion, IL-1 beta, TNF alpha, TGF beta 1 and 2 and ET-1 may p articipate in the regulation of bone resorption by stimulating IL-6 ex pression in HOC. Dexa inhibits the constitutive and cytokine stimulate d IL-6 expression, whereas there is no in vitro evidence that sex ster oids exert a major inhibitory effect on the osteoblastic secretion of IL-6 as demonstrated in a primary human bone cell model.