Role of cytokines in bone resorption - PubMed (original) (raw)

Review

Role of cytokines in bone resorption

S C Manolagas. Bone. 1995 Aug.

Abstract

It has been established during the past few years that interleukin(s)-1, -6, -11 (IL-1, IL-6, IL-11), and tumor necrosis factor (TNF) can stimulate osteoclast development and thereby the process of bone resorption. Moreover, upregulation of the production and/or action of IL-6 has been implicated in the pathogenesis of disease states characterized by excessive osteoclastic bone resorption, including the osteopenias associated with loss of either ovarian or testicular function. This article highlights this evidence and attempts to clarify the role of cytokines in the bone loss associated with gonadal deficiency. Specifically, it reviews data demonstrating that the protective effects of estrogens and androgens on the skeleton are mediated through their ability to inhibit IL-6 production. Both of these steroids exert their effects by inhibiting the transcriptional activity of the IL-6 gene promoter via mechanisms involving their respective specific receptors. Upon loss of gonadal function in either sex, there occurs an upregulation of osteoclast formation which is mediated by IL-6. Consistent with this, IL-6-deficient mice do not exhibit an increase in the formation of osteoclasts after ovariectomy or orchidectomy, and are protected from the bone loss caused by the loss of gonadal function in either sex. Even though these observations establish that IL-6 is an essential pathogenetic factor in the bone loss caused by gonadal deficiency, it remains unclear whether IL-6 is the sole pathogenetic factor or whether IL-1, TNF, and IL-11 may also be involved. However, in contrast to IL-6, these cytokines do not seem to be directly regulated by sex steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

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