Keratinocyte growth factor protects against Pseudomonas aeruginosa-inducedlung injury

We have previously reported that keratinocyte growth factor (KGF) attenuate s alpha -naphthylthiourea-induced lung injury by upregulating alveolar flui d transport. The objective of this study was to determine the effect of KGF pretreatment in Pseudomonas aeruginosa pneumonia. A 5% bovine albumin solu tion with 1 mu Ci of I-125-labeled human albumin was instilled into the air spaces 4 or 24 h after intratracheal instillation of P. aeruginosa, and th e concentration of unlabeled and labeled proteins in the distal air spaces over 1 h was used as an index of net alveolar fluid clearance. Alveolocapil lary barrier permeability was evaluated with an intravascular injection of 1 mCi of I-131-albumin. In early pneumonia, KGF increased lung liquid clear ance (LLC) compared with that in nonpretreated animals. In late pneumonia, LLC was significantly reduced in the absence of KGF but increased above the control value with KGF. KGF pretreatment increased the number of polymorph onuclear cells recovered in the bronchoalveolar lavage fluid and decreased bacterial pulmonary translocation. In conclusion, KGF restores normal alveo lar epithelial fluid transport during the acute phase of P. aeruginosa pneu monia and LLC in early and late pneumonia. Host response is also improved a s shown by the increase in the alveolar cellular response and the decrease in pulmonary translocation of bacteria.