Anti-TNF therapy for Crohn's disease.
Although the cause of Crohn's disease remains unknown considerable progress has been made in recent years to unravel the pathogenesis of the inflammatory processes seen in chronic idiopathic inflammatory bowel diseases (IBD). Th-1 lymphocytes seem to orchestrate the inflammation through the production of pro-inflammatory cytokines such as IFN-gamma, IL-1beta and tumor necrosis factor (TNF). After isolation and characterization of TNF and its two receptors (p55 and p75) detailed regulatory processes for transcription, secretion and post receptor actions of TNF are now rapidly being discovered. Genetically engineered monoclonal antibodies, specifically directed against TNF are only the first drugs acting against TNF, available for clinical use now in the treatment of Crohn's disease. A single IV injection of these antibodies produces very dramatic clinical, endoscopic and histological responses in a majority of refractory patients. More data on long term safety and the exact role in combination with standard therapies are being awaited. In the mean time, these drugs should be reserved for patients not responding to standard antiinflammatory therapy. The exciting "TNF story" very nicely illustrates how the benchmark of basic immunological research now provides us with very potent and rationally designed drugs. Expected and unexpected safety toxicity data should caution clinicians to a certain extent against too liberal use of these agents interfering with very basic physiological events.
D'Haens
Geert
G
Department of Gastroenterology at the University Hospital Gasthuisberg, Leuven, Belgium. geert.dhaens@uz.kuleuven.ac.be
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab