Effects of endogenous inflammation signals elicited by nerve growth factor, interferon-γ, and interleukin-4 on peripheral nerve regeneration

BACKGROUND: Large gap healing is a difficult issue in the recovery of peripheral nerve injury. The present study provides in vivo trials of silicone rubber chambers filled with collagen containing IFN-γ or IL-4 to bridge a 15 mm sciatic nerve defect in rats. Fillings of NGF and normal saline were used as the positive and negative controls. Neuronal electrophysiology, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide and histology of the regenerated nerves were evaluated. RESULTS: At the end of 6 weeks, animals from the groups of NGF and IL-4 had dramatic higher rates of successful regeneration (100 and 80%) across the wide gap as compared to the groups of IFN-γ and saline controls (30 and 40%). In addition, the NGF group had significantly higher NCV and shorter latency compared to IFN-γ group (P < 0.05). The IL-4 group recruited significantly more macrophages in the nerves as compared to the saline controls and the NGF-treated animals (P < 0.05). CONCLUSIONS: The current study demonstrated that NGF and IL-4 show potential growth-promoting capability for peripheral nerve regeneration. These fillings in the bridging conduits may modulate local inflammatory conditions affecting recovery of the nerves.