Tacrolimus Prevents the Development of Laryngotracheal Stenosis in the Novel Rat Model

Abstract

Objectives: Acquired laryngotracheal stenosis (LTS) is a challenging problem for otolaryngologists. Modulating the wound healing of airway mucosa is the key component for treating LTS. Drug-eluting stents (DESs) with immunosuppressants as Tacrolimus have been dominant for the treatment of coronary artery diseases in the interventional cardiology owing to their efficacy in significantly reducing restenosis. Several studies suggested Tacrolimus might potentially have inhibitory effects on airway stenosis as seen in coronary DESs. The objective of the present study is to determine whether immunosuppressants modulate the wound healing of airway mucosa and prevent obstructive airway disease in an acute injury animal model. Methods: The authors recently reported the novel reliable LTS model in rats, whose laryngotracheal mucosa was scraped with a nylon brush through the tracheostoma. Tacrolimus (0.2 or 1.0 mg/kg i.m.) was systemically administered for 5 days. The pathological changes at the airway mucosa and the tracheal lumen were assessed at 7 days after the scraping. The percentage of stenosis was calculated by image analysis software. Results: Both hyperplasia of airway epithelium and thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition provoked lumen stenosis. There was significant preventive effect on airway stenosis in the lower dose of Tacrolimus (0.2mg/kg) compared to brushing only group ( P < 0.05). The high dose of Tacrolimus group (1.0mg/kg) also showed a trend to potential protection of airway stenosis. Conclusions: This study suggests that the systemic immunosuppressive agent, Tacrolimus, has a preventive effect on LTS from mucosal injury of the airway.