title: Pro-inflammatory cytokines in cryptoglandular anal fistulas.
abstract: BACKGROUND
  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)-1β and tumor necrosis factor α (TNF-α).
  
  
  METHODS
  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-1β, IL-8, IL-10, IL-12p40, IL-17A, IL-18, IL-36 and TNF-α. The presence and frequencies of cytokine-producing cells in samples were quantitated.
  
  
  RESULTS
  The key finding was abundant expression of IL-1β in 93 % of the anal fistulas. Frequencies of IL-1β-producing cells were highest (>50 positive stained cells) in 7 % of the anal fistulas. Also, cytokines IL-8, IL-12p40 and TNF-α were present in respectively 70, 33 and 30 % of the anal fistulas.
  
  
  CONCLUSIONS
  IL-1β is expressed in the large majority of cryptoglandular anal fistulas, as well as several other pro-inflammatory cytokines.
authors.affiliation: Department of Surgery, Erasmus Medical Center Rotterdam, University Medical Center, Room H 181's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. r.vanonkelen@gmail.com.|Department of Immunology, Erasmus MC, University Medical Center, MS Center ErasMS, Rotterdam, The Netherlands. r.vanonkelen@gmail.com.
authors.forename: R S
authors.initials: RS
authors.lastname: van Onkelen
authors.affiliation: Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Gosselink
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, MS Center ErasMS, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Meurs
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, MS Center ErasMS, Rotterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Melief
authors.affiliation: Department of Surgery, Erasmus Medical Center Rotterdam, University Medical Center, Room H 181's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: W R
authors.initials: WR
authors.lastname: Schouten
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, MS Center ErasMS, Rotterdam, The Netherlands.|Department of Neuroscience, University Medical Center, University of Groningen, Groningen, The Netherlands.
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012003:Rectal Fistula / Q000378:metabolism* / Q000601:surgery*; D013524:Surgical Flaps; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta
keywords: Auto-inflammatory; Bacteria; Immunology; Microbiota; Perianal fistulas; Platelet-rich plasma