Crohn´s disease, a transmural inflammation of the gut, is associated with good childhood hygiene, frequent use of antibiotics before diagnosis, adherent or invasive mucosal bacteria and a break in the tolerance of luminal bacteria. A decrease or lack of mucosal peptide antibiotics, may play a central role in the aetiopathogenesis of Crohn's disease. The dysregulated adaptive immune system, may reflect only the primary break of the mucosal defence since the immune response is mostly directed against luminal bacteria. Crohn's disease patients with ileal involvement, as compared to controls and Crohn's disease patients without ileal disease, are characterized by a diminished expression of the ileal Paneth cell defensins. This decrease is even more pronounced in Crohn's disease patients with a mutation in the NOD2 gene, which is associated with Crohn's disease and ileal involvement. NOD2 is an intracellular peptidoglycan receptor and is expressed in Paneth cells. In contrast to ulcerative colitis, Crohn's disease of the colon is characterized by an impaired induction of human beta defensins 2 and 3. The hypothesis of an impaired mucosal antibacterial activity is also consistent with the benefit from antibiotic or probiotic treatment in certain disease states. For example, remission in ulcerative colitis may well be maintained by probiotic E. coli Nissle, similar to 5-aminosalicylates. On the other hand, initial reports suggest a role a parasite, trichuris suis, in treating active Crohn´s disease. Both have been shown to potently induce defensin synthesis so that, in the future, the immunosuppression used up to now may be replaced by agents inducing mucosal defense.

Literature:


(1) Wehkamp J, Fellermann K, Herrlinger KR, Baxmann S, Schmidt K, Schwind B, Duchrow M, Wohlschlager C, Feller AC, Stange EF. Human beta-defensin 2 but not beta-defensin 1 is expressed preferentially in colonic mucosa of inflammatory bowel disease. Eur J Gastroenterol Hepatol 2002; 14(7):745-752.
(2) Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger KR, Fellermann K, Schroeder JM, Stange EF. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003; 9(4):215-223.
(3) Wehkamp J, Schwind B, Herrlinger KR, Baxmann S, Schmidt K, Duchrow M, Wohlschlager C, Feller AC, Stange EF, Fellermann K. Innate immunity and colonic inflammation: enhanced expression of epithelial alpha-defensins. Dig Dis Sci 2002; 47(6):1349-1355.
(4) Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaeffeler E, Schlee M, Stallmach A, Noack F, Fritz P, Schroder JM, Bevins CL, Fellermann K, Stange EF. NOD2 (CARD15) mutations in Crohn´s disease are associated with diminished mucosal á-defensin expression. Gut, in press 2004.
(5) Fahlgren A, Hammarstrom S, Danielsson A, Hammarstrom ML. Increased expression of antimicrobial peptides and lysozyme in colonic epithelial cells of patients with ulcerative colitis. Clin Exp Immunol 2003; 131(1):90-101.
(6) Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S. Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 2003; 125(1):47-57.
(7) Hisamatsu T, Suzuki M, Reinecker HC, Nadeau WJ, McCormick BA, Podolsky DK. CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology 2003; 124(4):993-1000.
(8) Fellermann K, Wehkamp J, Herrlinger KR, Stange EF. Crohn´s disease: a defensin deficiency syndrome ? Eur J Gastroenterol Hepatol 2003; 15(6):627-634.

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