Tacrolimus impairs airway mucociliary clearance of rats.

OBJECTIVES: Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats. METHODS: Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus. After 7, 15 or 30 days of treatment, ten animals from each group were euthanized and the following parameters were studied: mucus transportability, CBF, mucociliary transport velocity (MCTV), and neutral and acid mucus production. RESULTS: There was a significant decrease in CBF (Control vs TAC: 7 days, p = 0.008; 15 days, p = 0.007; 30 days, p = 0.001) and MCTV (Control vs TAC: 7 days, p = 0.004; 15 days, p < 0.001; 30 days, p < 0.001) in all immunosuppressed animals. TAC therapy also caused an increase in acid mucus production at all treatment times (Control vs TAC: 7 days, p = 0.001; 15 days, p = 0.043; 30 days, p = 0.001). CONCLUSIONS: TAC impairs airway mucociliary clearance of rats.

Immunosuppression effects on airway mucociliary clearance: comparison between two triple therapies.

BACKGROUND: Tacrolimus and mycophenolate have now become the most widely used combination for maintenance immunosuppressive regimens after lung transplantation in comparison with cyclosporine and azathioprine. However, limited information is available with respect to their effects on cells, other than those from the immunologic compartment. We hypothesized that different triple therapies could have different effects on airway mucociliary clearance, playing an important role in respiratory infections observed after lung transplantation. METHODS: Ninety rats were assigned to three groups (n = 30 each): control = vehicle, therapy 1 = tacrolimus + mycophenolate + prednisone, and therapy 2 = cyclosporine + azathioprine + prednisone. After 7, 15, or 30 days of treatment by gavage, the animals were killed and the following parameters were studied: mucus transportability, ciliary beating frequency, mucociliary transport velocity, and neutral and acid mucus production. RESULTS: There was a significant decrease in ciliary beating frequency, mucociliary transport velocity, and neutral mucus production in all immunosuppressed animals; indeed, both therapies, mainly therapy 1, caused an increase in acid mucus production for as long as 15 days of treatment. CONCLUSIONS: Both triple therapies impaired airway mucociliary clearance of rats, but therapy 1 had a more deleterious effect. These data suggest that these undesirable effects can contribute to the high incidence of respiratory infections observed in patients undergoing lung transplantation.