KERATINOCYTE GROWTH-FACTOR ATTENUATES LUNG LEAK INDUCED BY ALPHA-NAPHTHYLTHIOUREA IN RATS

Objective: To investigate the effect of pretreatment with keratinocyte growth factor on acute permeability pulmonary edema. Design: Prospect ive, randomized, controlled animal study. Setting: University research laboratory. Subjects: Specific pathogen-free Sprague-Dawley rats. Int ervention: Acute permeability pulmonary edema was induced with an inje ction of alpha-naphthylthiourea, and lung leak was assessed in an isol ated perfused lung model over 180 mins, Leak was confirmed with wet/dr y lung weight ratios, and the alveolar fluid protein concentration was measured after bronchoalveolar ravage, The effect of pretreatment wit h keratinocyte growth factor (injected intratracheally 48 hrs before t he experiment) on alpha-naphthylthiourea-induced pulmonary edema was a ssessed (keratinocyte growth factor/alpha-naphthylithiourea group). Co ntrol groups (Control and keratinocyte growth factor/Control) were als o studied, Histopathology was performed for each of the four groups. M easurements and Main Results: The alpha-naphthylthiourea produced an a cute permeability pulmonary edema detected by lung leak over the 180-m in ex vivo period of monitoring the isolated perfused lung (leak = 8 /- 1 mL; wet/dry weight ratio 14.7 +/- 2; lavage protein 3.1 +/- 1 mg/ mL), Pretreatment with keratinocyte growth factor significantly attenu ated these parameters (leak = 2.3 +/- 0.4 mt; wet/dry weight ratio 7.1 +/- 0.5; lavage protein 0.28 +/- 0.03 mg/ mt), which were not signifi cantly different from the control group and the keratinocyte growth fa ctor/control group, Histopathology showed abundant type II pneumocyte hyperplasia in the lungs of animals pretreated with keratinocyte growt h factor, and marked pulmonary edema in animals pretreated with alpha- naphthylthiourea. Less edema was apparent in the keratinocyte growth f actor/alpha-naphthylithiourea group, All data are expressed as mean +/ - SEM. Conclusions: Pretreatment with keratinocyte growth factor signi ficantly attenuates pulmonary edema induced by alpha-naphthylthiourea, The mechanisms of this protection are likely related to type II pneum ocyte hyperplasia, but remain to be specifically elucidated.