Effect of immune cytokines on bone.

The effect of the bone resorptive cytokines IL-1 alpha, IL-1 beta, and TNF on bone formation was studied in an in vitro system. All three cytokines were profoundly inhibitory, with the rank order of potency IL-1 beta greater than IL-1 alpha greater than TNF. Inhibition was mediated by a depression of differentiated osteoblast functions, including alkaline phosphatase expression and matrix synthesis. Osteoblast proliferation was not affected. Bone formation inhibition was independent of PGE2 production, indicating a direct effect of cytokines on osteoblasts. High concentrations of IL-1 beta (10 U/ml) abrogated IGF-1-stimulated bone formation, providing evidence for the hypothesis that cytokines act as 'uncoupling factors'. Conversely, high concentrations of IGF-1 circumvented inhibition by IL-1 beta (0.1-1.0 U/ml). The interaction of cytokines and bone growth factors with osteoblasts are likely to be of critical importance in the regulation of bone mass at local inflammatory sites.