Infliximab and Etanercept Are Equally Effective in Reducing Enterocyte APOPTOSIS in Experimental Colitis [Abstract]

Infliximab and Etanercept Are Equally Effective in Reducing Enterocyte APOPTOSIS in Experimental Colitis

Walter Fries¹, Carmelo Muja², Carmela Crisafulli², Giuseppe Costantino¹, Giuseppe Longo¹, Salvatore Cuzzocrea^2,3, Emanuela Mazzon^2,3

1. Dipartimento di Medicina Interna e Terapia Medica, Sezione di Farmacologia, Università di Messina, Messina, Italy.
2. Dipartimento Clinico-Sperimentale di Medicina e Farmacologia, Sezione di Farmacologia, Università di Messina, Messina, Italy.
3. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy.

Loss of epithelial barrier integrity is considered an early step in the pathogenesis of Crohn's disease (CD), and the rate of enterocyte apoptosis is one of the determinants of the intestinal barrier function. Tumor necrosis factor-α (TNF-α), one of the major proinflammatory mediators in CD, is one of the extrinsic signals which initiate apoptosis of enterocytes. The aim of this study was to investigate the early effects of experimental colitis on enterocyte apoptosis, and the effects of two anti-TNF treatments, infliximab (IFX) and etanercept (ETC). In addition, the importance of receptor I for TNF was tested in TNFR-1^-/-mice.

Circulating TNF-α levels were effectively reduced by IFX and ETC (p<0.01, both) at 3 and 6 h. Apoptosis of the ileal enterocytes, assessed by TUNEL staining, staining for Fas-ligand, and bax, increased at 3 and 6h. These alterations were prevented by both anti-TNF strategies, and in TNFR-1^-/- animals. The anti-apoptotic protein Bcl-2 was expressed in the ileal epithelium under control conditions, but was suppressed in DNB-colitis. Expression of Bcl-2 was maintained in both anti-TNF treatments and TNFR-1^-/- mice.

DNB colitis induced a very early, rapid increase of enterocyte apoptosis. Both anti-TNF strategies, IFX and ETC, were equally effective in suppressing enterocyte apoptosis, most likely by inactivation of circulating TNF-α.

How to cite this article:
Fries W, Muja C, Crisafulli C, Costantino G, Longo G, Cuzzocrea S, Mazzon E. Infliximab and Etanercept Are Equally Effective in Reducing Enterocyte APOPTOSIS in Experimental Colitis. Int J Med Sci 2008; 5:169-180. Available from http://www.medsci.org/v05p0169.htm