Intravenous keratinocyte growth factor protects against experimental pulmonary injury.
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.
Amgen Preclinical Research, Thousand Oaks, California 91320-1789, USA.
J
J
Guo
E S
ES
Yi
A M
AM
Havill
I
I
Sarosi
L
L
Whitcomb
S
S
Yin
S C
SC
Middleton
P
P
Piguet
T R
TR
Ulich
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011510:Proteolipids / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011663:Pulmonary Surfactants / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012129:Respiratory Function Tests; D015431:Weight Loss / Q000187:drug effects
C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D001761:Bleomycin; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors