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Tacrolimus prevents laryngotracheal stenosis in an acute‐injury rat model
Author(s) -
Mizokami Daisuke,
Araki Koji,
Tanaka Nobuaki,
Suzuki Hiroshi,
Tomifuji Masayuki,
Yamashita Taku,
Matsushita Kazuyuki,
Shimada Hideaki,
Shiotani Akihiro
Publication year - 2015
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.25178
Subject(s) - tacrolimus , medicine , stenosis , airway , h&e stain , pathology , immunohistochemistry , hyperplasia , fibrosis , urology , gastroenterology , surgery , transplantation
Objectives/Hypothesis 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. Study Design 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. Level of Evidence NA Laryngoscope , 125:E210–E215, 2015