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. Material and methods. Fortyseven 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.