Keratinocyte growth factor ameliorates radiation- and bleomycin-induced lung injury and mortality

Eunhee S. Yi, Scott T. Williams, Hyesun Lee, Denise M. Malicki, Elaine M. Chin, Songmei Yin, John Tarpley, Thomas R. Ulich

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179 Scopus citations


Keratinocyte growth factor (KGF) is a growth factor for type II pneumocytes. Type H pneumocyte hyperplasia, a common reaction to lung injury, has been postulated to play an important role in lung repair. The potential protective effect of KGF was therefore studied in rat models of radiation- and bleomycin-induced lung injury. Intratracheal instillation of KGF (5 mg/kg) 72 and 48 hours before 18 Gy of bilateral thoracic irradiation did not significantly improve survival, although histology showed less pneumonitis and fibrosis in KGF-pretreated as compared 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 histological evidence of pulmonary fibrosis whereas the 8 surviving control rats exhibited severe respiratory distress. Finally, in the most lethal challenge to the lung, rats pretreated with intratracheal KGF or saline were challenged with a combination of bleomycin (1.5 U) and bilateral thoracic irradiation (18 Gy). KGF-pretreated rats did not begin 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 pulmonary injury and respiratory death are ameliorated by KGF pretreatment, suggesting a protective role for KGF-induced type II pneumocyte proliferation in lung injury.

Original languageEnglish (US)
Pages (from-to)1963-1970
Number of pages8
JournalAmerican Journal of Pathology
Issue number6
StatePublished - Dec 21 1996

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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