title: Crohn's disease: a defensin deficiency syndrome?
abstract: This comprehensive review promotes the novel concept that a defensin deficiency, i.e. lack of mucosal peptide antibiotics, may play a pivotal role in the aetiopathogenesis of Crohn's disease. Such an impaired function of this chemical barrier is consistent with the epidemiological relationship of good domestic hygiene with the incidence of inflammatory bowel diseases. The disregulated adaptive immune system, formerly believed to be the major cause in the development of Crohn's disease, may reflect only the primary break of the mucosal defence since the immune response is mostly directed against lumenal bacteria. Recent work has identified five different defensins expressed in colonic mucosa. In contrast to ulcerative colitis, Crohn's disease is characterised by an impaired induction of human beta defensins 2 and 3. This deficient induction may be due to changes in the intracellular transcription by NFkappaB and the intracellular peptidoglycan receptor NOD2, mutated in Crohn's disease. These findings are consistent with the mucosal attachment of lumenal bacteria in inflammatory bowel diseases and the frequent occurrence of other infectious agents. The hypothesis of an impaired mucosal antibacterial activity is also consistent with the benefit from antibiotic or probiotic treatment in certain inflammatory bowel disease states.
authors.affiliation: Department of Internal Medicine I, Robert Bosch Krankenhaus, Stuttgart, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Fellermann
authors.forename: Jan
authors.initials: J
authors.lastname: Wehkamp
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Herrlinger
authors.forename: Eduard F
authors.initials: EF
authors.lastname: Stange
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000150:complications; D003424:Crohn Disease / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D023082:Defensins / Q000172:deficiency* / Q000502:physiology; D006801:Humans; D006920:Hygiene; D019936:Probiotics / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D000900:Anti-Bacterial Agents; D023082:Defensins