Antimicrobial peptides in chronic anal fistula epithelium.
OBJECTIVE
Anal fistulas are the result of chronic infection of an intersphincteric gland. Despite the passage through mesenchymal tissue, fistulas seldom lead to systemic infection. Antimicrobial peptides are secreted by a variety of epithelia, belonging to the innate immune system and are potential factors contributing to infection control. The aim of this study was to investigate whether epithelium is present in the fistulas and what the origin might be.


METHODS
Forty-seven chronic anal fistulas from patients, excluding Crohn's disease, were compared with healthy rectal and perianal control tissue. Expression of antimicrobial peptide mRNA was analysed by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Tissue was further studied by cytokine and cytokeratin staining.


RESULTS
Chronic anal fistulas express high levels of hBD-2 and hBD-3 and the newly identified antimicrobial peptides RNase7 and psoriasin compared to rectal mucosa from control patients. Perianal skin has almost identical levels of RNase7 and psoriasin expression to those in fistulas. IL-1b and IL-8 were the only cytokines detectable in fistulas. Fistulas are lined with squamous epithelium that expresses identical cytokeratines as skin.


CONCLUSIONS
Epithelialization and local production of antimicrobial peptides in anal fistulas serve as defence mechanisms to prevent local and systemic infection by microbes from faeces passing through the fistula tract.
Kiehne
Karlheinz
K
I. Department of Internal Medicine, Universitätsklinikum Schleswig Holstein, Schittenhelmstr, Germany. kkiehne@lmed.unkiel.de
Fincke
Alexander
A
Brunke
Gabriele
G
Lange
Tobias
T
Fölsch
Ulrich R
UR
Herzig
Karl-Heinz
KH
D000328:Adult; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002908:Chronic Disease; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012003:Rectal Fistula / Q000378:metabolism* / Q000473:pathology; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism*; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D012867:Skin / Q000378:metabolism / Q000473:pathology; D023083:beta-Defensins / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D023083:beta-Defensins; D007633:Keratins; D012260:Ribonucleases; C470000:Ribonuclease 7