Defensin expression in chronic pouchitis in patients with ulcerative colitis or familial adenomatous polyposis coli.
OBJECTIVE
Pouchitis develops in ileoanal pouches in up to 50% of patients with ulcerative colitis during the first 10 years after pouch surgery while being rare in patients after proctocolectomy for familial adenomatous polyposis coli (FAP) syndrome. Defensins are major components of the innate immune system and play a significant role in gastrointestinal microbial homeostasis. Pouch defensin and cytokine expression were correlated with states of pouch inflammation to study their role in pouchitis.


METHODS
Patients with ulcerative colitis and FAP syndrome were stratified into groups with pouches after surgery, pouches without or with pouchitis. Biopsies from terminal ileum from a healthy intestine or from normal terminal ileum of patients with ulcerative colitis served as controls. mRNA from pouches and controls was analysed for defensin and cytokine expression.


RESULTS
Expression of defensins was increased in all pouches immediately after surgery, compared to ileum of controls. Initially, pouches in ulcerative colitis revealed higher defensin expression than FAP pouches. Defensin expression declined in both patient groups and increased again slightly in pouchitis in patients with ulcerative colitis. FAP pouches without pouchitis had strong expression of beta-defensin hBD-1, while all other defensins remained at low levels. Cytokine expression in ulcerative colitis pouches was high, while FAP pouches showed moderately elevated cytokines only after surgery.


CONCLUSIONS
Development of pouchitis correlates with decreased defensin expression in ulcerative colitis in addition to high expression of cytokines. The low incidence of pouchitis in FAP pouches correlates with increased expression of hBD-1 beta-defensin in association with low cytokine levels.
I. Department of Internal Medicine, Universitatsklinikum Schleswig Holstein, Schittenhelmstr. 12, Kiel 24105, Germany. kkiehne@1med.uni-kiel.de
Karlheinz
K
Kiehne
Gabriele
G
Brunke
Franziska
F
Wegner
Tomas
T
Banasiewicz
Ulrich R
UR
Folsch
Karl-Heinz
KH
Herzig
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D039021:Colonic Pouches / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D023082:Defensins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007082:Ileum / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D007107:Immune System / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019449:Pouchitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016737:Proctocolectomy, Restorative; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D023084:alpha-Defensins / Q000096:biosynthesis / Q000235:genetics; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics
D016207:Cytokines; D023082:Defensins; D012333:RNA, Messenger; D023084:alpha-Defensins; D023083:beta-Defensins