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Front Neurol. 2019 Jan 29;10:30. doi: 10.3389/fneur.2019.00030. eCollection 2019.

Transient Receptor Potential Vanilloid 1 Modulates Central Inflammation in Multiple Sclerosis.

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Unit of Neurology and Neurorehabilitation, IRCCS Neuromed, Pozzilli, Italy.
Laboratory of Synaptic Immunopathology, Department of Systems Medicine, Tor Vergata University, Rome, Italy.
Clinica Neurologica, Università Politecnica delle Marche, Ancona, Italy.
Laboratory of Neuroimmunology and Synaptic Plasticity, University & IRCCS San Raffaele, Rome, Italy.
Servizio di Statistica Medica & Information Technology, Fondazione Fatebenefratelli per la Ricerca e la Formazione Sanitaria e Sociale, Rome, Italy.
Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute, Milan, Italy.


Introduction: Disease course of multiple sclerosis (MS) is negatively influenced by proinflammatory molecules released by activated T and B lymphocytes and local immune cells. The endovanilloid system plays different physiological functions, and preclinical data suggest that transient receptor potential vanilloid type 1 (TRPV1) could modulate neuroinflammation in this disorder. Methods: The effect of TRPV1 activation on the release of two main proinflammatory cytokines, tumor necrosis factor (TNF) and interleukin (IL)-6, was explored in activated microglial cells. Furthermore, in a group of 132 MS patients, the association between the cerebrospinal fluid (CSF) levels of TNF and IL-6 and a single nucleotide polymorphisms (SNP) influencing TRPV1 protein expression and function (rs222747) was assessed. Results: In in vitro experiments, TRPV1 stimulation by capsaicin significantly reduced TNF and IL-6 release by activated microglial cells. Moreover, the anti-inflammatory effect of TRPV1 activation was confirmed by another TRPV1 agonist, the resiniferatoxin (RTX), whose effects were significantly inhibited by the TRPV1 antagonist, 5-iodoresiniferatoxin (5-IRTX). Vice versa, BV2 pre-treatment with 5-IRTX increased the inflammatory response induced by LPS. Moreover, in MS patients, a significant association emerged between TRPV1 SNP rs222747 and CSF TNF levels. In particular, the presence of a G allele, known to result in increased TRPV1 protein expression and function, was associated to lower CSF levels of TNF. Conclusions: Our results indicate that TRPV1 influences central inflammation in MS by regulating cytokine release by activated microglial cells. The modulation of the endovanilloid system may represent a useful approach to contrast neuroinflammation in MS.


IL-6; TNF; capsaicin; endocannabinoids; microglia; neuroinflammation

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