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Am J Physiol Lung Cell Mol Physiol 275: L800-L805, 1998;
1040-0605/98 $5.00
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Vol. 275, Issue 4, L800-L805, October 1998

Intravenous keratinocyte growth factor protects against experimental pulmonary injury

Jane Guo1, Eunhee S. Yi2, Andrew M. Havill1, Ildiko Sarosi1, Lane Whitcomb1, Songmei Yin1, Scot C. Middleton1, Pierre Piguet1, and Thomas R. Ulich1

1 Amgen Preclinical Research, Thousand Oaks 91320-1789; and 2 San Diego School of Medicine, University of California, San Diego, California 92103

Keratinocyte growth factor (KGF) administered by intratracheal instillation is well documented to stimulate the proliferation of alveolar and bronchial cells. In the present study, intravenous KGF was also shown to stimulate the proliferation of alveolar and bronchial cells in mice and rats, although to a lesser degree than intratracheal KGF. Despite the decreased potency of intravenous KGF on pulmonary cell 5-bromo-2'-deoxyuridine incorporation compared with intratracheal KGF, intravenous KGF was very effective in preventing experimental bleomycin-induced pulmonary dysfunction, weight loss, and mortality in either mice or rats and experimental hyperoxia-induced mortality in mice. The effectiveness of intravenous administration of KGF in preventing lung injury suggests that the mechanisms of the protective effect of KGF may involve more than pulmonary cell proliferation and also suggests the potential use of systemic KGF for clinical trials in settings of pulmonary injury.

bleomycin; hyperoxia


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