Anti-TNF antibodies do not induce the apoptosis of lamina propria mononuclear cells in uninflamed intestinal tissue in patients with Crohn's disease

Abstract

It is not known if anti-tumor necrosis factor (anti-TNF) agents provoke only apoptosis of lamina propria mononuclear cells (LPMC) engaged in inflammatory processes or whether it's a general phenomenon concerning all LPMC. In this study we carried out an immunohistochemical analysis of the expression of several apoptosis-related proteins (active caspase-3, Bax, Bcl-2, Fas, TNFR1, CD4, and CD8) in uninflamed mucosa in Crohn's disease (CD) patients treated with anti-TNF agents. 16 CD patients (mean age 34 ± 11, mean disease duration 7 ± 5 years) were included in the study. 10 patients were treated with infliximab and 6 - with adalimumab. The expression of active caspase 3, Bax, Bcl-2, Fas, TNFR1 and CD8 in LPMC did not change significantly after the therapy. We concluded that anti-TNF antibodies did not promote LPMC apoptosis in uninflamed tissues. This is in contrast to the phenomena observed in inflamed tissues. These data show that anti-TNF antibodies rather restore the susceptibility to apoptosis of LPMC in inflamed areas of the gut in CD, than directly induce LPMC apoptosis; otherwise the anti-TNF antibodies should have also induced apoptosis in the uninflamed mucosa.