The biologics anakinra and etanercept prevent cytokine-induced growth retardation in cultured fetal rat metatarsal bones.

BACKGROUND/AIMS: Chronic inflammation during childhood often leads to impaired bone growth and reduced adult height. Proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α synergistically impair bone growth in vitro. We hypothesized that biologic agents may rescue bones from cytokine-induced growth impairment and that insulin growth factor (IGF)-I may potentiate such an effect.

METHODOLOGY

Metatarsal bones from fetal Sprague-Dawley rats (19-20 days p.c.) were treated with IL-1β plus TNF-α, or the combination of these cytokines with anakinra (IL-1 receptor antagonist), etanercept (TNF-inhibitor) and/or IGF-I. The bones were measured and growth expressed as percent increase in bone length over the 7-day culture period.

RESULTS

When exposed to IL-1β plus TNF-α (10 + 10 ng/ml), bone growth was markedly suppressed (6.6 ± 1.4 vs. 50.6 ± 2.5% in control bones; p < 0.001). The growth of cytokine exposed bones (IL-1β plus TNF-α) was dose-dependently rescued by anakinra (0.05-500 μg/ml) or etanercept (0.5-500 μg/ml); at the highest concentrations, growth was similar as in control bones never exposed to cytokines. Also when combining IGF-I (100 ng/ml) and relatively low concentrations of anakinra (0.05 μg/ml) or etanercept (5 μg/ml), growth was rescued in an additive way.

CONCLUSION

Etanercept and anakinra efficiently and dose-dependently prevent cytokine-induced bone growth impairment, and combination with IGF-I further improves bone growth.