title: The impact of hydrocortisone treatment on neutrophil gelatinase-associated lipocalin release in porcine endotoxemic shock.
abstract: BACKGROUND
  A key feature of sepsis is systemic inflammatory activation that could be counteracted by steroids. In this experimental model of systemic inflammation, we sought to investigate whether septic neutrophil activation, evaluated by the plasma levels of neutrophil gelatinase-associated protein (NGAL), is modulated by the timing of hydrocortisone treatment.
  
  
  METHODS
  Sixteen anesthetized pigs were allocated to one of four equally sized groups. Three of these groups received endotoxin at 2 μg × kg-1× h-1for 6 h so as to induce endotoxemic shock. Hydrocortisone (5 mg × kg-1) was administered intravenously before endotoxemic challenge, or at the onset of endotoxemic shock. Endotoxemic pigs not receiving hydrocortisone and non-endotoxemic pigs served as control groups. Physiologic variables, hematology, and biochemistry, including plasma NGAL, were measured repeatedly.
  
  
  RESULTS
  Hydrocortisone treatment prior to endotoxemia attenuated some inflammatory, hematological, circulatory, and metabolic manifestations of shock (i.e., higher white blood cell count, higher mean arterial pressure, lower heart rate and mean pulmonary arterial pressure, higher left ventricular stroke work index, higher base excess). Endotoxemic shock increased plasma NGAL (p < 0.001). In pigs given hydrocortisone before the endotoxin infusion, plasma NGAL was lower as compared to those given hydrocortisone at endotoxemic shock (p < 0.05). Plasma NGAL levels correlated inversely to neutrophil granulocyte counts (rho = -0.65) but not to urine output (rho = -0.10) at the end of the experiment.
  
  
  CONCLUSIONS
  The increase in plasma NGAL is counteracted by hydrocortisone administration prior to endotoxemia; concomitantly, this treatment was associated with less expressed circulatory derangement. Urine NGAL did not differ between the groups, suggesting that the NGAL response was not primarily related to kidney injury.
authors.affiliation: Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Söderberg
authors.affiliation: Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden. miklos.lipcsey@surgsci.uu.se.|Hedenstierna laboratory, Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. miklos.lipcsey@surgsci.uu.se.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-1976-4129
authors.initials: M
authors.lastname: Lipcsey
keywords: Endotoxins; Hydrocortisone; NGAL; Neutrophils; Pigs; Sepsis