Immunomodulatory effects of etanercept in an experimental model of spinal cord injury.
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-alpha (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, 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-alpha and interleukin-1beta); 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-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.
Genovese
Tiziana
T
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina Italy.
Mazzon
Emanuela
E
Crisafulli
Concetta
C
Di Paola
Rosanna
R
Muià
Carmelo
C
Bramanti
Placido
P
Cuzzocrea
Salvatore
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000032:analysis; D017341:Etanidazole / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000032:analysis; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis
D007155:Immunologic Factors; D007375:Interleukin-1; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D017341:Etanidazole; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2