title: Ulinastatin improves pulmonary function in severe burn-induced acute lung injury by attenuating inflammatory response.
abstract: BACKGROUND
  Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the systemic inflammatory response induced by endotoxin and improves myocardial function during ischemic shock and reperfusion.
  
  
  METHODS
  Rats received full-thickness burn wounds to 30% total body surface area followed by delayed resuscitation. The treatment group received 50,000 U/kg of ulinastatin and the burn group was given vehicle only. A sham group was not burned but otherwise was treated identically. After killing, blood and lung samples were harvested for histology and measurement of inflammatory mediators.
  
  
  RESULTS
  Administration of ulinastatin significantly decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1β, -6, and -8 both locally and systemically in burn-injured rats. The secretion of neutrophil elastase and myeloperoxidase in the lung and the expression of intercellular adhesion molecule-1 on the surface of lung epithelium were inhibited by ulinastatin. Ulinastatin also reduced the increase in pulmonary microvascular permeability. Consistent with these findings, ulinastatin ameliorated the lung edema and pulmonary oxygenation in burn-injured rats.
  
  
  CONCLUSIONS
  These results indicate that the inhibitory effects of ulinastatin on inflammatory mediator production, neutrophil activation, and microvascular permeability are associated with the recovery of pulmonary functions in severe burn-induced acute lung injury and suggest that ulinastatin may serve as a potential therapeutic administration in critical burn care.
authors.affiliation: Department of Burns and Plastic Surgery, No. 3 People's Hospital, Shanghai, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.forename: Peng
authors.initials: P
authors.lastname: Xu
authors.forename: Chuan
authors.initials: C
authors.lastname: Gu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Fu
authors.forename: Wei-Rong
authors.initials: WR
authors.lastname: Yu
authors.forename: Min
authors.initials: M
authors.lastname: Yao
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D002056:Burns / Q000150:complications* / Q000503:physiopathology; D004487:Edema / Q000188:drug therapy; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014361:Trypsin Inhibitors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D019272:Leukocyte Elastase; C028665:urinastatin