A Step Forward toward the Clinical Application of Palifermin for Acute Respiratory Distress Syndrome?

摘要

Keratinocyte growth factor (KGF), also called fibroblast growth factor (FGF)-7, is a potent epithelial cell mitogen of the FGF family that functions as a paracrine mediator of mesenchymal-epithelial communication. KGF is produced by fibroblasts and endothelial cells, and exerts effects on epithelial cells by binding the epithelial-restricted FGFR2 receptor. Several key observations have highlighted potentially useful roles for exogenous KGF in the management of patients with acute respiratory distress syndrome (ARDS). These observations include the finding that KGF expression is suppressed in early ARDS and also that KGF may exert potentially beneficial effects on lung epithelial cells by promoting alveolar type Ⅱ (ATⅡ) cell proliferation , migration , survival , surfactant production , and ion transport and alveolar fluid clearance . These and other observations formed the basis of subsequent studies in animal models of ARDS, where exogenously applied (usually as an intratracheal pretreatment) KGF protected against lung injury induced by hyperoxia , bilateral thoracic irradiation and intratracheal bleomycin , and intratracheal hydrochloric acid , among other insults. This protection was often accompanied by improved mortality in the KGF-treated group. The translational potential of KGF administration in the context of ARDS has been further supported by encouraging results obtained with a truncated human KGF produced in Escherichia coli, marketed commercially as palifermin (Kepivance; Biovitrum, Stockholm, Sweden), in the management of oral mucositis during leukemia chemotherapy, where palifermin has proven to be safe and well tolerated .