Keratinocyte growth factor (KGF) prevents lung injury induced by radiation alone or combined radiation and bleomycin treatment

KGF, a growth factor for type II pneumocytes in vivo and in vitro, has been shown to prevent bleomycin-induced lung injury in rats. In one experiment, rats were injected with intratracheal (i.t.) KGF (1.25 mg) or sterile saline at 48 and 24 hours prior to 18 Gy of bilateral thoracic irradiation. Survival rates at 75 days after thoracic irradiation were 36.4% in KGF-treated and 35.7% in saline-treated rats. Histologie examination of the lungs upon death showed significantly less pneumonitis and fibrosis in KGF-treated as compared to saline-treated rats. Despite the lack of apparent distress in the surviving rats at 75 days, all 5 salinepretreated surviving rats revealed significantly greater pneumonitis and pulmonary fibrosis as evaluated by semiquantitative histologie examination as compared to KGF-pretreated rats, of which only one showed significant lung histopathology. In a second experiment, rats pretreated with i.t. KGF or saline at 72 and -48 hours received 1.5 units of i.t. bleomycin shortly followed by 18 Gy of bilateral thoracic irradiation. Saline-pretreated rats underwent severe respiratory difficulty and weight loss as early as 5 days. KGF-pretreated rats, in contrast, showed no signs of distress and have significantly higher body weights (224.6 ± 8.9 g vs 183.7 ± 3.9 g in saline-treated rats, p<0.0001) at day 5. KGF-pretreated rats showed normal lung histology as opposed to severe pneumonitis and fibrosis in saline-pretreated rats at day 7. All saline-pretreated rats died after the radiation and bleomycin injection (average days of survivals 5.6 ±6.5). In contrast, 50.0% of KGF-pretreated rats (9/18) have survived for greater than 70 days. KGFpretreated rats who died nevertheless survived significantly longer (60.1 ±4.3 days; p<0.0001) than control rats. In conclusion, radiation with or without bleomycin-induced lung injury is ameliorated by KGF pretrealment, suggesting a protective role for KGF-induced type II pneumocyte proliferation.