Effect of immune Cytokines on Bone

Abstract

The effect of the bone resprptive cytokines IL-1L, IL-1β, 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-1β > IL-1α > 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-1β (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-1β (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.