Interleukin-6 inhibits bone formation in vitro.

Interleukin-6 (IL-6) is a pluripotent cytokine which is made by osteoblasts, but its role in bone metabolism is uncertain. The aim of this study was to test the effect of IL-6 on bone formation in vitro using a nodule-forming assay. Osteoblast-enriched calvaria cells were isolated from 2-day-old Sprague-Dawley rats and cultured in the presence of 10(-8) M dexamethasone. After 2 days, calvaria cells were treated with recombinant human IL-6 for 72 h, washed and maintained for a further 18 days before fixation. IL-6 caused a dose-dependent inhibition of bone nodule formation, with a maximum reduction of 53% with 5000 U/ml IL-6. IL-6 also inhibited alkaline phosphatase activity in a dose-dependent manner (e.g. control: 114 +/- 9.2; IL-6: 68 +/- 10.6 nmol p-nitrophenol (pNP)/mg/min). IL-6 did not affect cell numbers during early cell growth up to 6 days but caused a small but significant reduction in cell number at confluence (8 days). These results demonstrate that IL-6 inhibits bone nodule formation by rat calvaria cells in vitro and suggest that IL-6 may inhibit osteoblast differentiation.