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.
Publication types
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Controlled Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Adalimumab
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Adult
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized / pharmacology*
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Antibodies, Monoclonal, Humanized / therapeutic use
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Apoptosis / drug effects*
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CD4 Antigens / genetics
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CD4 Antigens / metabolism
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CD8 Antigens / genetics
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CD8 Antigens / metabolism
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Crohn Disease / drug therapy*
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Crohn Disease / metabolism
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Crohn Disease / pathology
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Female
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Humans
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Infliximab
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Intestinal Mucosa / drug effects*
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Leukocytes, Mononuclear / drug effects*
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Leukocytes, Mononuclear / metabolism
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Male
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Tumor Necrosis Factor, Type I / genetics
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Receptors, Tumor Necrosis Factor, Type I / metabolism
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
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fas Receptor / genetics
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fas Receptor / metabolism
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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CD4 Antigens
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CD8 Antigens
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FAS protein, human
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Tumor Necrosis Factor, Type I
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bcl-2-Associated X Protein
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fas Receptor
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Infliximab
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Caspase 3
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Adalimumab