title: Comparison of experimental lung injury from acute renal failure with injury due to sepsis.
abstract: BACKGROUND
  Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) coexist frequently, and the mortality rate of this combination is very high. It is well established that cytokines and chemokines play a major role in the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown to be protective against ARDS.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the pathophysiology of ARDS in two different conditions, sepsis and ARF.
  
  
  METHODS
  We examined five different rat animal models including sham-operated control, sepsis and three ARF models induced by renal ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal pedicles. We analyzed pulmonary histology, pulmonary vascular permeability, cellular infiltration, and expression of cytokines, chemokines and HSPs.
  
  
  RESULTS
  Like sepsis, the three forms of ARF led to ARDS, as manifested by increased pulmonary vascular permeability and histological changes consistent with ARDS. On the other hand, ARF and sepsis differed in that ARF was associated with markedly lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary expression of tumor necrosis factor-alpha increased in sepsis, cytokine-induced neutrophil chemoattractant 2 increased in nephrectomized rats indicating that different inflammatory mediators were involved in the injury mechanism. Finally, pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8 and HSP90 was significantly different between the two conditions.
  
  
  CONCLUSIONS
  We conclude that the pathophysiology of ARDS following ARF is distinct from that in sepsis. ARF-induced ARDS is characterized by a low level of cellular infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a discrete expression profile of HSPs.
authors.affiliation: Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Do Jin
authors.initials: DJ
authors.lastname: Kim
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Mee Rie
authors.initials: MR
authors.lastname: Sheen
authors.forename: Un Sil
authors.initials: US
authors.lastname: Jeon
authors.forename: Seung Whan
authors.initials: SW
authors.lastname: Kim
authors.forename: Eun Suk
authors.initials: ES
authors.lastname: Koh
authors.forename: Seung Kyoon
authors.initials: SK
authors.lastname: Woo
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications* / Q000378:metabolism; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019743:Chemokines, CXC; C513294:Cxcl3 protein, rat; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha