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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 22, 2005; DOI: 10.1124/jpet.105.097188

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Received for publication October 14, 2005.
Revised November 18, 2005.
Accepted for publication November 21, 2005.

Immunomodulatory Effects Of Etanercept In An Experimental Model Of Spinal Cord Injury

Tiziana Genovese 1, Emanuela Mazzon 1, Concetta Crisafulli 1, Rosanna Di Paola 1, Carmelo Muia 1, Placido Bramanti 1, Salvatore Cuzzocrea 1*

1 University of Messina

* Address correspondence to: E-mail: salvator{at}unime.it

Abstract

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 TNF-{alpha} 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, 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) neutrophils infiltration (MPO evaluation), (3) iNOS, nitrotyrosine, COX2, and cytokines expression (TNF-{alpha} and IL-1{beta}), (4) and apoptosis (TUNEL staining and Bax and Bcl-2 expression). In a separate set of experiment we have also clearly demonstrated that TNF-{alpha} 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.


Key words: Etanercept, TNF-a, apoptosis, free radical, inflammation, spinal cord injury


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