The impact of chronic inflammation on the growing skeleton: Lessons from interleukin-6 transgenic mice

Background: Chronic inflammatory diseases in children are associated with impairment of linear growth and bone mineral accrual. In addition to poor nutrition, reduced mobility and glucocorticoid treatment, several observations in patients suggest that inflammation itself may have a direct detrimental effect on the growing skeletal system. Among the various inflammatory cytokines produced during the inflammatory response, data in animals suggest that interleukin-6 (IL-6) may mediate the effects of inflammation on the developing skeleton. Mice overexpressing IL-6 during the prepubertal stage show stunted growth, abnormalities of the insulin-like growth factor I system, defective growth plates, delayed development of ossification centres, uncoupling of osteoblast and osteoclast activity and defective ossification. These changes appear to mirror the features observed in children with chronic inflammatory diseases. Conclusions: The tissue, cellular and molecular abnormalities reviewed provide a rationale for therapeutic approaches aimed at correcting the detrimental effects of inflammation on the developing skeletal system.