Departments of Experimental Internal Medicine and Gastroenterology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands
Address for correspondence: Jan M. H. Van den Brande, Departments of Experimental Internal Medicine and Gastroenterology, G3-130, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Voice: (31)-20-566 5910; fax: (31)-20-697 7192.
J.M.vandenbrande{at}amc.uva.nl
Ann. N.Y. Acad. Sci. 973: 166-180 (2002).
Apoptosis is one of the most important regulatory mechanisms
in immunological homeostasis. Disturbances in the apoptotic
pathways lead to autoimmune disease. Crohn's disease is a chronic
inflammatory bowel disease of unknown origin, which seems to
be mediated by excessive T cell-mediated immunity. Recently,
disturbances in apoptotic pathways of lamina propria T lymphocytes
of patients with Crohn's disease have been identified. In the
uninflamed, normal intestinal mucosa, lamina propria (LP) T
cells are susceptible to activation-induced cell death, but
these cells show a resistance to apoptosis based on several
disturbances compared to controls. Recently, intriguing data
were published using cytokine-targeted therapy (anti-IL12, anti-IL6
receptor, anti-TNF). Actually, these medications restored mucosal
immunological imbalance by inducing apoptosis of the LP T cells
and seemed to be beneficial in models of Crohn's disease. In
this review, mechanisms of immunological homeostasis will be
discussed. We will also discuss the fascinating new results
of cytokine-targeted therapy in animal models of Crohn's disease
and the effects of these drugs in patients with Crohn's disease.
