title: Reduction of pulmonary inflammatory response by erythropoietin in a rat model of endotoxaemia.
abstract: BACKGROUND
  Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.
  
  
  METHODS
  A total of 32 male Sprague-Dawley rats were randomly assigned to four groups: saline group, erythropoietin + saline group, saline + lipopolysaccharide group and erythropoietin + lipopolysaccharide group. Rats were treated with erythropoietin (3000 U/kg, i.p.) or saline, 30 minutes prior to lipopolysaccharide administration (6 mg/kg, i.v.). Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry (W/D) ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha (TNF-alpha) as well as interleukin 1 beta (IL-1beta) levels in lungs were measured. The pulmonary expression of nuclear factor kappaB (NF-kappaB) p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance (ANOVA).
  
  
  RESULTS
  The lung tissues from the saline + lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin + lipopolysaccharide group. The W/D ratio increased significantly in the saline + lipopolysaccharide group (5.75 +/- 0.22) as compared with the saline group (3.85 +/- 0.20) (P < 0.01), which was significantly reduced in the erythropoietin + lipopolysaccharide group (4.50 +/- 0.35) (P < 0.01). Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline + lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin + lipopolysaccharide group. The TNF-alpha level of pulmonary tissue increased significantly in the saline + lipopolysaccharide group ((9.80 +/- 0.82) pg/mg protein) compared with the saline group ((4.20 +/- 0.42) pg/mg protein, P < 0.01). However, the increase of TNF-alpha level of pulmonary tissue was significantly reduced in the erythropoietin + lipopolysaccharide group ((6.50 +/- 0.66) pg/mg protein, P < 0.01). Similarly, pulmonary IL-1beta levels were elevated markedly in the saline + lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin + lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline + lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin + lipopolysaccharide group.
  
  
  CONCLUSIONS
  Erythropoietin attenuates pulmonary inflammation and suppresses TNF-alpha and IL-1beta overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-kappaB.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: You
authors.initials: Y
authors.lastname: Shang
authors.forename: Yuan-Xu
authors.initials: YX
authors.lastname: Jiang
authors.forename: San-Peng
authors.initials: SP
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhou-Yang
authors.initials: ZY
authors.lastname: Wu
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Yuan
authors.forename: Shang-Long
authors.initials: SL
authors.lastname: Yao
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D019446:Endotoxemia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D008315:Malondialdehyde; D009195:Peroxidase