title: Selective immunomodulation in patients with inflammatory bowel disease--future therapy or reality?
abstract: Knowledge of the aetiology and pathogenesis of the inflammation in ulcerative colitis and Crohn's disease is still insufficient. It is thought that some antigen is the trigger which induces a chain of immune reactions but the origin of this antigen has not so far been elucidated. In theory, an antigen-presenting cell forms a complex with endotoxin-derived peptides as antigen. T-helper lymphocytes recognize this complex, are activated and start to produce cytokines. For inflammatory bowel diseases (IBD) the most important cytokines identified are interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), gamma-interferon (G-IFN), and tumor necrosis factor-alpha (TNF-alpha). Inhibition of these cytokines can be achieved by administration of cyclosporine, which inhibits the function of T-helper lymphocytes. Orally, intravenously, and locally administered cyclosporine is able to improve the disease activity in ulcerative colitis and Crohn's disease, but its use is limited because of side-effects. The novel immunosuppressant FK506 has comparable actions to cyclosporine in regulating cytokine production and may even be more effective than cyclosporine. The receptor antagonist of IL-1 (IL-1ra) competitively binds to the IL-1 receptor located on several lymphocytes. Treatment of animals with IL-1ra has been successful and clinical trials using recombinant IL-1ra are underway in IBD. Antibodies against alphaIL-2r have also been used successfully in animal studies. No experience with this substance has been obtained in man. The use of alpha-interferon seems to be effective in some patients with Crohn's disease. CD4 and CD8 molecules on lymphocytes are needed to form the interaction between antigen, antigen-presenting cell, and lymphocytes. Specific monoclonal antibodies against CD4 are successfully used in patients with active ulcerative colitis and Crohn's disease. TNF-alpha shares many of the proinflammatory activities of IL-1. In preliminary studies, especially in patients with Crohn's disease, the effects of the administration of antibodies to TNA-alpha were excellent.
authors.affiliation: Department of Gastroenterology-Hepatology, University Hospital Leiden, Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: van Hogezand
authors.forename: H W
authors.initials: HW
authors.lastname: Verspaget
mesh_terms: D003093:Colitis, Ulcerative / Q000628:therapy; D003424:Crohn Disease / Q000628:therapy; D016572:Cyclosporine / Q000627:therapeutic use; D016207:Cytokines / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000628:therapy*; D007413:Intestinal Mucosa / Q000276:immunology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D016572:Cyclosporine