title: In Situ Deactivation of Interleukin-6 Enhances Early Peripheral Nerve Regeneration in a Murine Injury Model.
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.
  
  
  CONCLUSIONS
  In situ IL-6 receptor inhibition and IL-6(-/-) nerve grafting enhance early peripheral nerve regeneration in an acute murine injury model.
authors.affiliation: Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koulaxouzidis
authors.affiliation: Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Reim
authors.affiliation: Department of Dermatology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Fluhr
authors.affiliation: Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany.
authors.forename: Filip
authors.initials: F
authors.lastname: Simunovic
authors.affiliation: Department of Plastic and Hand Surgery, University of Freiburg Medical Centre, Freiburg, Germany.
authors.forename: G Bjoern
authors.initials: GB
authors.lastname: Stark
authors.affiliation: Department of Plastic and Reconstructive Surgery, Interdisciplinary Breast Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Witzel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000502:physiology*; D016067:Nerve Transfer / Q000379:methods*; D012584:Sciatic Nerve / Q000637:transplantation; D000093242:Interleukin-6 Inhibitors
chemical_list: D000093242:Interleukin-6 Inhibitors