QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.097188v1 316/3/1006    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Genovese, T. Articles by Cuzzocrea, S. Search for Related Content PubMed PubMed Citation Articles by Genovese, T. Articles by Cuzzocrea, S.

INFLAMMATION AND IMMUNOPHARMACOLOGY

Immunomodulatory Effects of Etanercept in an Experimental Model of Spinal Cord Injury

Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy (T.G., E.M., C.C., R.D.P., C.M., S.C.); and Centro per lo Studio ed il Trattamento dei Neurolesi Lungodegenti, School of Medicine, University of Messina, Messina, Italy (P.B.)

Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate for the first time the therapeutic efficacy of in vivo inhibition of tumor necrosis factor- (TNF-) in experimental model of spinal cord trauma, which was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T₅–T₈ laminectomy. Spinal cord injury in mice resulted in severe trauma characterized by edema, neutrophil infiltration, and cytokine production that it is followed by recruitment of other inflammatory cells, such as production of a range of inflammation mediators, tissue damage, apoptosis, and disease. Treatment of the mice with etanercept significantly reduced the degree of 1) spinal cord inflammation and tissue injury (histological score); 2) neutrophil infiltration (myeloperoxidase evaluation); 3) inducible nitric-oxide synthase, nitrotyrosine, cyclooxygenase-2, and cytokines expression (TNF- and interleukin-1); and 4) apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a separate set of experiment, we have also clearly demonstrated that TNF- inhibitor significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury events associated with spinal cord trauma.

Address correspondence to: Dr. Salvatore Cuzzocrea, Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina Italy. E-mail: salvator{at}unime.it

This article has been cited by other articles:

				T. Genovese, E. Esposito, E. Mazzon, R. D. Paola, R. Meli, P. Bramanti, D. Piomelli, A. Calignano, and S. Cuzzocrea Effects of Palmitoylethanolamide on Signaling Pathways Implicated in the Development of Spinal Cord Injury J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 12 - 23. [Abstract] [Full Text] [PDF]

				T. Genovese, E. Esposito, E. Mazzon, C. Muia, R. Di Paola, R. Meli, P. Bramanti, and S. Cuzzocrea Evidence for the Role of Mitogen-Activated Protein Kinase Signaling Pathways in the Development of Spinal Cord Injury J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 100 - 114. [Abstract] [Full Text] [PDF]

				W. Fries, C. Muja, C. Crisafulli, S. Cuzzocrea, and E. Mazzon Dynamics of enterocyte tight junctions: effect of experimental colitis and two different anti-TNF strategies Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G938 - G947. [Abstract] [Full Text] [PDF]