Abstract
Background Systemic alteration of interleukin-6 (IL-6) influences peripheral nerve regeneration. We investigated the potential influences of in situ (at the coaptation site) IL-6 modulation in a peripheral-nerve-transection/sciatic-nerve-graft in vivo model.
Methods We quantified the elongation of regenerating axons, the number of arborizing axons, and the number of branches per arborizing axon 7 days after the injury in mice expressing axonal fluorescent proteins (thy-1-YFP mice). Sciatic nerves from nonexpressing mice (C57Bl6 or IL-6−/− mice) were grafted into those expressing yellow fluorescent protein. We altered the in situ IL-6 concentration by loading a topical gelatin sponge with an inhibiting IL-6 receptor antibody or IL-6 combined with a soluble IL-6 receptor. Sciatic nerves from IL-6−/− mice were grafted into an additional group. The contralateral sham-operated side served as control in all the groups.
Results Axonal elongation increased significantly with the in situ application of the IL-6 receptor antibody, while topical IL-6 significantly reduced the regeneration distance. The number of arborizing axons increased significantly in nerves grafted from IL-6−/− mice, whereas branches per arborizing axons remained stable.
Conclusion In situ IL-6 receptor inhibition and IL-6−/− nerve grafting enhance early peripheral nerve regeneration in an acute murine injury model.
Keywords
interleukin-6 - peripheral nerve regeneration - thy-1-YFP mice - branching - nerve injury - sciatic nerve - arborization
