Pro-inflammatory cytokines in cryptoglandular anal fistulas

Sphincter-preserving procedures for the treatment of transsphincteric fistulas fail in at least one out of every three patients. It has been suggested that failure is due to ongoing disease in the remaining fistula tract. Cytokines play an important role in inflammation. At present, biologicals targeting cytokines are available. Therefore, detection and identification of cytokines in anal fistulas might have implications for future treatment modalities. The objective of the present study was to assess local production of a selected panel of cytokines in anal fistulas, including pro-inflammatory interleukin (IL)-1 beta and tumor necrosis factor alpha (TNF-alpha). Fistula tract tissue was obtained from 27 patients with a transsphincteric fistula of cryptoglandular origin who underwent flap repair, ligation of the intersphincteric fistula tract or a combination of both procedures. Patients with a rectovaginal fistula or a fistula due to Crohn's disease were excluded. Frozen tissue samples were sectioned and stained using advanced immuno-enzyme staining methods for detection of selected cytokines, IL-1 beta, IL-8, IL-10, IL-12p40, IL-17A, IL-18, IL-36 and TNF-alpha. The presence and frequencies of cytokine-producing cells in samples were quantitated. The key finding was abundant expression of IL-1 beta in 93 % of the anal fistulas. Frequencies of IL-1 beta-producing cells were highest (> 50 positive stained cells) in 7 % of the anal fistulas. Also, cytokines IL-8, IL-12p40 and TNF-alpha were present in respectively 70, 33 and 30 % of the anal fistulas. IL-1 beta is expressed in the large majority of cryptoglandular anal fistulas, as well as several other pro-inflammatory cytokines.