Tacrolimus Causes Airway Mucociliary Clearance Impairment

Abstract

Purpose: According to ISHLT Registry, the vast majority of lung transplant patients receive a tacrolimus-based maintenance immuno-suppressant therapy. However, its side effects on respiratory tract are not very well studied. We hypothesized that tacrolimus could impair airway mucociliary clearance. Methods and Materials: Twenty Wistar rats were assigned into two groups: Control (n¼10): saline solution; and TAC (n=10): tacrolimus (1 mg/kg/day). After 15 days of therapy by gavage, animals were killed and in situ mucociliary transport velocity (MCTV) and ciliary beating frequency (CBF) were measured by microscopic direct view of airway ciliated epithelium. Mucus production by goblet cells was quantified in periodic acid Schiff and alcian blue stained slides of the tracheobron-chial tissue. This study was support by São Paulo Research Foundation - Fapesp. Results: There was a significant decrease in MCTV (1.77 ± 0.50 and 0.73 ± 0.34 mm/min, Control and TAC, respectively, p<0.001) and CBF (15.06 ± 1.31 and 13.17 ± 1.47 Hertz, Control and TAC, respectively, p<0.001) in all TAC-treated animals. Indeed, tacrolimus caused an over production of mucus from airway goblet cells (12.78 ± 6.92 and 21.27 ± 7.86%, Control and TAC, respectively; p=0.007). Conclusions: Our study showed that TAC plays an important role on the impairment of the mucociliary clearance either by decreasing CBF and MCTV or by increasing mucus production. This impairment can be related with the high level of respiratory infection observed during the first 30 days after lung transplantation and must receive good attention from clinicians.