Impact of Anti-Tumor Necrosis Factor (TNF) Antibodies on the T-lymphocyte and Macrophage Cooperation in Crohn Disease

Impact of Anti-Tumor Necrosis Factor (TNF) Antibodies on the T-lymphocyte and Macrophage Cooperation in Crohn Disease

The aim of this research is to study Crohn disease patients before and after anti-TNF, the cooperation between lamina propria T-lymphocytes and macrophages, through the expression of co-signalisation molecules and their ligands, the production of cytokines participating in this cooperation, and the potential role of regulatory T lymphocytes.

Crohn disease is an inflammatory disease and its frequency has been increasing over the last 25 years. The physiopathology involves a failure in the negative regulatory mechanisms of the inflammatory responses in the intestines, along with an excessive production of TNF-α by T-lymphocytes and macrophages of the lamina propria. Anti-TNF-α antibodies usually give good therapeutic results, in particular in patients who are resistent or dependant on steroids. Nevertheless, in Crohn disease, the destructive T-lymphocytes - macrophage interactions, their inhibition by anti-TNFα, and the impact of these antibodies on cellular signaling remain largely unknown. Two groups of 10 patients with active Crohn disease, with or without azathioprine, and requiring the start of anti-TNF treatment are included in this study. Rectosigmoïdal biopsies and blood tests will be done before starting the treatment and after 10 weeks of treatment. Surface antigens, cytokines and cellular molecules and the number of apoptotic cells will be analyzed by FACS, and the quantification of RNA will be analyzed by RT-PCR. This will therefore enable us to study, before and after anti-TNF-α, in patients treated or not with azathioprine, on intestinal and blood lymphocytes, the production of cytokines involved in the lymphocyte-macrophage interaction, and the potential role of regulatory T cells.

Relative variation (%) in apoptotic cells calculated according to the formula: (% of induced apoptotic cells) - (% of spontaneous apoptotic cells)

Inclusion Criteria: patient older than 18 social security active Crohn disease defined by a CDAI > 250 sigmoïdal and/or rectal lesions requiring treatment by infliximab having never received any anti-TNF treatment a negative pregnancy test for women prescription of efficient contraception for women, having started at least a month before beginning the study, and throughout the duration of the study acceptance to participate in this research and having signed the consent form not participating in any other study Exclusion Criteria: consent withdrawal the halt of infliximab treatment

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