Immunomodulatory and Anti-oxidative Effect of the Direct TRPV1 Receptor Agonist Capsaicin on Schwann Cells (4686)

Objective: In the present study, we describe an anti-inflammatory and anti-oxidative influence of capsaicin on Schwann cells (SCs) in an in vitro setting. Background: The active component of chili pepper, capsaicin, is the direct agonist of the transient receptor potential channel vanilloid subfamily member-1. The effect of nutritive factors on chronic inflammatory demyelinating polyneuropathy (CIDP), a chronic inflammatory disease of the peripheral nervous system has not been described before. Its anti-inflammatory effect in the animal model experimental autoimmune neuritis (EAN) has been previously demonstrated from our group. Design/Methods: We analyzed the effect of capsaicin on Schwann cells’ gene expression pattern, major histocompatibility complex class II (MHC-II) expression, and H2O2 induced oxidative stress. Furthermore, the effect of capsaicin on myelination was examined in a SC-dorsal root ganglia (DRG)-coculture by myelin basic protein staining. Finally, in order to investigate the isolated effect of capsaicin on SCs in EAN pathology, we transplant naive and capsaicin pre-treated SCs intrathecally in EAN immunized rats and analyzed clinical presentation, electrophysiological parameters, and cytokine expression in the sciatic nerve. Results: In SC culture, incubation with capsaicin significantly reduces interferon gamma induced MHC-II production as well as toll-like receptor 4 and intercellular adhesion molecule 1 mRNA expression. Calcitonin gene-related peptide mRNA production is significantly up-regulated after capsaicin treatment. Capsaicin reduced H2O2 induced oxidative stress in SC in a preventive, but not therapeutic setting. In a SC-DRG-coculture, capsaicin does not affect myelination rate. After intrathecally transplantation of naive and capsaicin pre-treated SCs in EAN immunized rats, naive, but not capsaicin pre-treated intrathecally SCs ameliorated EAN pathology in rats. Conclusions: We demonstrate an immunomodulatory and anti-oxidative effect of capsaicin in a SC culture. These results are in concordance with previous data showing an anti-inflammatory effect of capsaicin, which might be highly relevant for CIDP patients. Disclosure: Dr. Pitarokoili has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with KP received travel funding and speaker honoraria from Biogen Idec, Novartis and Bayer Schering Pharma and funding from the Ruhr-University, Bochum (FORUM-Program).Dr. Blush has nothing to disclose. Dr. Motte has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with JM received travel grants from Biogen idec, Novartis AG, Teva and Eisai GmbH, his research is funded by Klaus Tschira Foundation and Ruhr-University, Bochum (FoRUM-program).Dr. Sgodzai has nothing to disclose. Dr. Bachir has nothing to disclose. Dr. Klimas has nothing to disclose. Dr. Ambrosius has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis and Celgene GmbH. Dr. Ambrosius has received research support from FORUM Anschubfinanzierung, Medizinische, and Faktultat Ruhr-Universitat Bochum. Dr. Gold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Diseases, Experimental Neurology and the Journal of Neuroimmunology. Dr. Gold has received research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis.Dr. Ellrichmann has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with GE, Biogen Idec, TEVA Pharma, Bayer Healthcare, Roche, Almirall, and Novartis Pharma.Dr. Gruter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme and Biogen Idec.