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Differential gene expression of cytokines and neurotrophic factors in nerve and skin of patients with peripheral neuropathies

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Abstract

Pathophysiologically relevant alterations in cytokine and neurotrophic factor levels have been reported in neuropathy subtypes. We characterized gene expression profiles of pro- and anti-inflammatory cytokines and neurotrophic factors in nerve and skin samples of patients with neuropathies of different etiologies. We prospectively studied 133 patients with neuropathies and compared data between subtypes and with healthy controls. All patients underwent sural nerve and/or skin punch biopsy at the lateral thigh and lower leg; controls received skin punch biopsies. Gene expression of pro- and anti-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF, IL-10), neurotrophic factors (BDNF, NGF, NT3, TrkA), and erythropoietin with the erythropoietin receptor (Epo, EpoR) was analyzed. Sural nerve gene expression of the investigated cytokines and neurotrophic factors did not differ between neuropathies of different etiologies; however, IL-6 (p < 0.01) and IL-10 (p < 0.05) expression was higher in painful compared to painless neuropathies. Skin IL-6 and IL-10 gene expression was increased in patients compared to controls (p < 0.05), and IL-10 expression was higher in lower leg skin of patients with non-inflammatory neuropathies compared to inflammatory neuropathies (p < 0.05). Proximal and distal skin neurotrophic factor and Epo gene expression of patients with neuropathies was reduced compared to controls (NGF, NT3, Epo; p < 0.05). Neuropathies are associated with an increase in cytokine expression and a decrease in neurotrophic factor expression including nerve and skin.

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Acknowledgments

Expert technical help by B. Broll, B. Dekant, and S. Mildner is gratefully acknowledged. The study was supported by the Bundesministerium für Bildung und Forschung (BMBF), Deutscher Forschungsverbund Neuropathischer Schmerz (DFNS), and by intramural funds of the University of Würzburg. This work is part of the doctoral thesis of N. Riediger.

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The authors declare that they have no conflicts of interest.

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  1. Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Germany

    Nurcan Üçeyler, Nadja Riediger, Waldemar Kafke & Claudia Sommer

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  1. Nurcan Üçeyler
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  2. Nadja Riediger
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Correspondence to Nurcan Üçeyler.

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Üçeyler, N., Riediger, N., Kafke, W. et al. Differential gene expression of cytokines and neurotrophic factors in nerve and skin of patients with peripheral neuropathies. J Neurol 262, 203–212 (2015). https://doi.org/10.1007/s00415-014-7556-8

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