Ulinastatin reduces pathogenesis of phosgene-induced acute lung injury in rats.
Phosgene (CG) is an industrial chemical used to make plastics, rubbers, dyestuff, and pesticides. Although the inhalation of CG is relatively uncommon, its accidental exposure can lead to acute lung injury (ALI). Ulinastatin, a urinary trypsin inhibitor, has been emerged to use for the treatment of acute inflammatory state of a number of organs including the lung. In this study, we examined the pathogenic changes in the lungs after the inhalation of CG gas and also examined the effect of ulinastatin treatment in reversing these changes in rats. We found that the rats exposed to CG gas at a dose of 5.0 g/m(3) for 5 min led to ALI after 6 h. The signs of lung injury include pulmonary edema, hemorrhage, and cellular infiltration in pulmonary alveoli. In addition, interleukin-15 (IL-15) and intercellular adhesion molecule-1 (ICAM-1) were significantly increased in CG-inhaled animals. Ulinastatin administration at 1 h postexposure significantly reduced the intensity of all the pathological changes in the lungs of these CG-exposed animals. Ulinastatin at a dose of 400 U/g was shown to decrease the total number of cells in bronchoalveolar lavage fluid and the levels of IL-15 and ICAM-1 in the serum. We also found that the structure of the lung was protected by ulinastatin treatment. Thus, our data suggest that ulinastatin can be used as an effective drug for the treatment of CG-induced ALI. The serum levels of IL-15 and ICAM-1 can be used as the markers of lung injury after exposure to CG and may also serve as useful therapeutic targets at an early stage. The effects of long-term treatment of ulinastatin and the mechanisms by which ulinastatin decreases the infiltration of blood cells and reduces cytokines need further investigation.
Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China Medical Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China guoxiong.xu@fudan.edu.cn j1999sh@yahoo.com.cn.
Jie
J
Shen
Center of Emergency and Intensive Care Unit, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China Medical Center of Chemical Injury, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
Zhengyi
Z
Gan
Department of Chemical Defense Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, People's Republic of China.
Jie
J
Zhao
Department of Chemical Defense Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, People's Republic of China.
Liming
L
Zhang
Center Laboratory, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China.
Guoxiong
G
Xu
D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D019409:Interleukin-15 / Q000097:blood; D008297:Male; D010705:Phosgene / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D006023:Glycoproteins; D019409:Interleukin-15; D010705:Phosgene; D018799:Intercellular Adhesion Molecule-1; C028665:urinastatin