Cytokine and anti-cytokine therapies for inflammatory bowel disease.
Although the pathogenesis of inflammatory bowel disease (IBD) remains elusive, it appears that there is chronic activation of the immune and inflammatory cascade in genetically susceptible individuals. Current disease management guidelines have therefore focused on the use of anti-inflammatory agents, aminosalicylates and corticosteroids. These conventional therapies continue to be a first choice in the management of IBD. Immunomodulators, such as azathioprine, 6-mercaptopurine, methotrexate or cyclosporin, are demonstrating increasing importance against steroid-resistant and steroid-dependent patients. However, some patients are still refractory to these therapies. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Other immunosuppressive agents including FK506 and thalidomide have expanded the choice of medical therapies available for certain subgroups of patients. Furthermore, biological therapies have begun to assume a prominent role. Studies with chimeric monoclonal anti-TNF-alpha antibody treatment have been reported with dramatic successes. However, observations in larger numbers of treated patients are needed to explicate fully the safety of or risks posed by this agent such as developing lymphoma, or other malignancies. Another anti-inflammatory cytokine-therapy includes anti anti-IL-6R, anti-IL-12 or toxin-conjugated anti IL-7R, recombinant cytokines (IL-10 or IL-11). Given the diversity of proinflammatory products under its control, NF-kappaB may be viewed as a master switch in lymphocytes and macrophages, regulating inflammation and immunity. Although some of them still need more confirmatory studies, those immune therapies will provide new insights into cell-based and gene-based treatment against IBD in near future.
Ogata
Haruhiko
H
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hibi
Toshifumi
T
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology; D005753:Gastric Mucosa / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology; D015851:Interleukin-7 / Q000037:antagonists & inhibitors / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D015851:Interleukin-7; D014409:Tumor Necrosis Factor-alpha