Treating Crohn's disease by inducing T lymphocyte apoptosis.
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.
Van Den Brande
Jan M H
JM
Department of Experimental Internal Medicine, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands. vandenbrande@amc.uva.nl
Peppelenbosch
Maikel P
MP
Van Deventer
Sander J H
SJ
D017209:Apoptosis / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12