Cyclosporin A reduces airway mucus secretion and mucociliary clearance in rats.
OBJECTIVE
To assay the effects of cyclosporin A on mucus secretion from goblet cells and on mucociliary transport in situ in rats.


METHODS
Twenty-one male Wistar rats were assigned to 3 groups: control (n = 5), saline (n = 8), and cyclosporin A (n = 8). After 30 days of drug therapy, the rats were killed, and the lungs were removed from the thoracic cavity. Mucus samples were collected, and the transport rate was evaluated in vitro using a bullfrog palate model. Mucociliary transport was timed in situ by direct view of particles trapped on the mucus moving across the respiratory tract. Finally, the amount of stored mucins in the goblet cells of the respiratory epithelium was measured.


RESULTS
Drug dosage measurements showed that cyclosporine blood concentration at the moment the rats were killed was 1246.57 +/- 563.88 ng/mL. The in vitro transport rate was significantly lower (P < .001) in the cyclosporin A-treated group. Also, the in-situ mucociliary transport rate was decreased in all cyclosporin A-treated animals when compared to the saline group (P = .02). Mucus quantity measurements showed a significant decrease on both acid (P = .01) and neutral (P = .02) mucus production from goblet cells in the animals submitted to cyclosporin A therapy. The correlation between the percentage of total mucus and in vitro transport rate was positive and significant (r = 0.706, P < .001), as was the correlation between the percentage of total mucus and the in situ mucociliary transport rate (r = 0.688, P = .001).


CONCLUSIONS
This study shows that cyclosporin A plays an important role in the impairment of the mucociliary clearance in rats by reducing both acid and neutral mucus production from goblet cells and causing a decrease in the mucociliary transport velocity.
Pazetti
Rogerio
R
Thoracic Surgery Service, Hospital das Clinicas, University of Sao Paulo, Sao Paulo, SP, Brazil. rogeriopazetti@yahoo.com.br
Pego-Fernandes
Paulo Manuel
PM
Ranzani
Otavio Tavares
OT
Parra
Edwin Roger
ER
Lorenzi-Filho
Geraldo
G
Jatene
Fabio B
FB
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D007166:Immunosuppressive Agents; D016572:Cyclosporine