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J Reconstr Microsurg 2015; 31(07): 508-515
DOI: 10.1055/s-0035-1555114
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

In Situ Deactivation of Interleukin-6 Enhances Early Peripheral Nerve Regeneration in a Murine Injury Model

Georgios Koulaxouzidis
1   Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany
,
Gernot Reim
1   Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany
,
Joachim W. Fluhr
2   Department of Dermatology and Allergology, Charité–Universitätsmedizin Berlin, Berlin, Germany
,
Filip Simunovic
1   Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany
,
G. Bjoern Stark
1   Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany
,
Christian Witzel
3   Department of Plastic and Reconstructive Surgery, Interdisciplinary Breast Center, Charité–Universitätsmedizin Berlin, Berlin, Germany
› Author Affiliations
Further Information

Publication History

29 December 2014

25 April 2015

Publication Date:
26 June 2015 (online)

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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
 

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