title: Tacrolimus prevents laryngotracheal stenosis in an acute-injury rat model.
abstract: OBJECTIVE
  Acquired laryngotracheal stenosis is a challenging problem for otolaryngologists. Several studies suggest tacrolimus may inhibit post-transplant airway stenosis that occurs with coronary drug-eluting stents. The objective of the present study was to determine whether tacrolimus modulates wound healing of the airway mucosa and prevents laryngotracheal stenosis in an acute injury animal model.
  
  
  METHODS
  Basic science.
  
  
  METHODS
  The laryngotracheal mucosa of rats was scraped with a nylon brush through the tracheostoma. Tacrolimus (0.2 mg/kg or 1.0 mg/kg) was systemically administered intramuscularly for 5 days. Nine days after scraping, the pathological changes and the degree of stenosis were assessed by hematoxylin and eosin staining or by immunohistochemical staining for nuclear factor of activated T cell and interleukin 2.
  
  
  RESULTS
  Lumen stenosis resulted from hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition. There was a significant preventive effect on airway stenosis at the tracheal and cricoid levels in the low-dose (0.2 mg/kg) tacrolimus-treated animals, compared to the untreated animals (P < .05). This effect was insignificant with treatment by high-dose tacrolimus (1.0 mg/kg). Immunohistochemistry showed that, after tacrolimus treatment, the expressions of nuclear factor of activated T cell and interleukin 2 were downregulated in submucosal fibroblasts, neovascular cells, and glandular cells.
  
  
  CONCLUSIONS
  This study suggests that low-dose systemic tacrolimus has a preventive effect on laryngotracheal stenosis by inhibiting the activation of immune cells in the injured airway mucosa via the calcineurin/nuclear factor of activated T cell/interleukin 2 pathway.
  
  
  METHODS
  NA.
authors: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Daisuke
authors: D
authors: Mizokami
authors: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Koji
authors: K
authors: Araki
authors: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Nobuaki
authors: N
authors: Tanaka
authors: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Hiroshi
authors: H
authors: Suzuki
authors: Masayuki
authors: M
authors: Tomifuji
authors: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Taku
authors: T
authors: Yamashita
authors: Department of Molecular Diagnosis, Division of Clinical Genetics and Proteomics, Graduate School of Medicine, Chiba University, Chiba City, Chiba, Japan.
authors: Kazuyuki
authors: K
authors: Matsushita
authors: Department of Surgery, Toho University School of Medicine, Ota-Ku, Tokyo, Japan.
authors: Hideaki
authors: H
authors: Shimada
authors: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors: Akihiro
authors: A
authors: Shiotani
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007829:Laryngostenosis / Q000209:etiology / Q000517:prevention & control*; D007830:Larynx / Q000293:injuries; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000627:therapeutic use*; D014132:Trachea / Q000293:injuries; D014135:Tracheal Stenosis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D065095:Calcineurin Inhibitors; D016559:Tacrolimus
keywords: Calcineurin inhibitor; immunosuppressive agent; laryngotracheal stenosis; rat; tacrolimus