title: Insulin therapy induces changes in the inflammatory response in a murine 2-hit model.
abstract: Post-traumatic complications commonly seen on intensive care units include sepsis and associated disorders, which are accompanied by alterations in inflammatory cytokine expression patterns and in activation of neutrophils. Hyperglycaemia, often occurring after trauma and sepsis, is a further risk factor for morbidity and mortality among critically ill people. Clinical investigations have suggested that strict glycaemic control by insulin titration reduces overall mortality. This study aimed to further elucidate the pathophysiological and immunomodulative actions of insulin. Femoral fracture was induced in a murine model, followed by 1h of haemorrhage. Two days after the first hit, sepsis was induced by caecal ligation and puncture (CLP). In control animals, laparotomy only was performed. Insulin in two different concentrations (10IU or 20IU) or vehicle was administered daily. Insulin therapy was associated with improvement of clinical parameters, slightly improved survival rates and, in lungs and liver, fewer infiltrating neutrophils and reduced IL-6 and IL-10 mRNA expression. These results suggested that, in this animal model, insulin had a direct anti-inflammatory effect that was independent of modulation of blood glucose levels.
authors.affiliation: Department of Trauma Surgery, Hannover Medical School, Carl-Neuberg Strasse-1, Hannover, Germany. barkhausen.tanja@mh-hannover.de
authors.forename: Tanja
authors.initials: T
authors.lastname: Barkhausen
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.forename: Frank
authors.initials: F
authors.lastname: Hildebrand
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
authors.forename: Christian
authors.initials: C
authors.lastname: Krettek
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D005264:Femoral Fractures / Q000150:complications*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008099:Liver; D008168:Lung; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology; D015996:Survival Rate
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin