Impact of Anti-TNF Antibodies on the T-lymphocyte and Macrophage Cooperation in the Crohn Disease
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
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Relative variation (%) in apoptotic cells calculated according to the formula: (% of induced apoptotic cells) - (% of spontaneous apoptotic cells)
before treatment and 10 weeks after treatment
Xavier Hébuterne, Professor
Centre Hospitalier Universitaire
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
06 - PP - 2006