KERATINOCYTE GROWTH-FACTOR AMELIORATES RADIATION-INDUCED AND BLEOMYCIN-INDUCED LUNG INJURY AND MORTALITY

Keratinocyte growth factor (KGF) is a growth factor for type II pneumo cytes. Type II pneumocyte hyperplasia, a common reaction to lung injur y, has been postulated to play an important role in lung repair. The p otential protective effect of KGF was therefore studied in rat models of radiation- and bleomycin-induced lung injury. Intratracheal instill ation of KGF (5 mg/kg) 72 and 48 hours before 18 Gy of bilateral thora cic irradiation did not significantly improve survival, although histo logy showed less pneumonitis and fibrosis in KGF-pretreated as compare d with control-irradiated rats. Intratracheal pretreatment with KGF in rats receiving intratracheal bleomycin (2.5 U) improved survival at 3 weeks to 100% (20/20 rats) from 40% (8.20 rats) in controls. All KGF- pretreated rats receiving bleomycin were well at 3 weeks and without h istological evidence of pulmonary fibrosis whereas the 8 surviving con trol rats exhibited severe respiratory distress. Finally, in the most lethal challenge to the lung, rats pretreated with intratracheal KGF o r saline were challenged with a combination of blemoycin (1.5 U) and b ilateral thoracic irradiation (18 Gy). KGF-pretreated rats did not beg in to die or show signs of respiratory distress until 7 weeks, whereas all saline-pretreated control rats receiving radiation and bleomycin died within approximately 4 weeks with severe respiratory distress and weight loss. In conclusion, radiation- and bleomycin-induced pulmonar y injury and respiratory death are ameliorated by KGF pretreatment, su ggesting a protective role for KGF-induced type II pneumocyte prolifer ation in lung injury.