title: Erythropoietin does not attenuate renal dysfunction or inflammation in a porcine model of endotoxemia.
abstract: BACKGROUND
  Erythropoietin (EPO) is a multifunctional cytokine with anti-apoptotic, anti-inflammatory, and organ protective effects. EPO protects against ischemia-reperfusion injuries, and recent reports suggest that EPO also prevents organ dysfunction in experimental sepsis. The aims of this study were to determine whether EPO prevents endotoxemia-induced organ dysfunction in a porcine model and to characterize the immunomodulatory and anti-apoptotic effects of EPO.
  
  
  METHODS
  Twenty-eight pigs were randomly assigned to three groups: (1) endotoxemia treated with EPO 5000 IU/kg, (2) endotoxemia treated with placebo, and (3) a sham group anesthetized and submitted to sham operation without treatment. A laparotomy was performed, and a flow probe was placed around the left renal artery, which allowed renal blood flow (RBF) measurements. Endotoxemia was induced by an infusion of lipopolysaccharide. After 2 h, the infusion was reduced to a maintenance dose and the animals were fluid resuscitated. The glomerular filtration rate (GFR), RBF, renal oxygen consumption, and plasma cytokines [interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha] were analyzed. Renal biopsies were analyzed for cytokine content and apoptosis.
  
  
  RESULTS
  Endotoxemia elicited impaired renal function, estimated as GFR, and increased the levels of renal apoptotic cells, with no modifying effect of EPO. Furthermore, EPO had no effect on RBF, renal oxygen consumption, or the systemic hemodynamic response to endotoxemia. EPO did not modify the inflammatory response, measured as changes in cytokine levels in plasma and organs.
  
  
  CONCLUSIONS
  EPO did not confer renal protection in this fluid-resuscitated porcine model of endotoxemia, and EPO did not modify the inflammatory response.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark. solling@ki.au.dk
authors.forename: C
authors.initials: C
authors.lastname: Sølling
authors.forename: A T
authors.initials: AT
authors.lastname: Christensen
authors.forename: U
authors.initials: U
authors.lastname: Nygaard
authors.forename: S
authors.initials: S
authors.lastname: Krag
authors.forename: J
authors.initials: J
authors.lastname: Frøkiaer
authors.forename: L
authors.initials: L
authors.lastname: Wogensen
authors.forename: J
authors.initials: J
authors.lastname: Krog
authors.forename: E K
authors.initials: EK
authors.lastname: Tønnesen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications* / Q000188:drug therapy*; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D007677:Kidney Function Tests; D008070:Lipopolysaccharides; D010101:Oxygen Consumption / Q000502:physiology; D011994:Recombinant Proteins; D012079:Renal Circulation / Q000187:drug effects; D012151:Resuscitation; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D053148:Caspase 3