title: Hyperglycemia enhances the cytokine production and oxidative responses to a low but not high dose of endotoxin in rats.
abstract: OBJECTIVE
  The aim of this study was to investigate whether hyperglycemia enhances the systemic inflammatory response and oxidative stress induced by endotoxin.
  
  
  METHODS
  Laboratory investigation.
  
  
  METHODS
  University medical school.
  
  
  METHODS
  Forty-one male Sprague-Dawley rats.
  
  
  METHODS
  A hyperglycemic condition was produced in rats by glucose clamp for 3 hrs. Immediately on stopping the glucose infusion, animals received different doses of endotoxin injection (0, 0.2, or 1 mg/kg), and then blood glucose concentration was monitored over the ensuing 2 hrs. At the end of 2 hrs, levels of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, corticosterone, and alpha-1 acid glycoprotein were determined in serum, and malondialdehyde and total glutathione content were determined in the liver.
  
  
  RESULTS
  Over the 2-hr period, blood glucose concentrations returned to normal in initially hyperglycemic rats. However, the levels of cytokines, corticosterone, and alpha-1 acid glycoprotein were significantly higher in these animals compared with nonhyperglycemic controls, demonstrating an extended effect of prior hyperglycemia on markers of systemic inflammation. With low-dose (0.2 mg/kg) but not high-dose (1 mg/kg) endotoxin administration, hyperglycemic animals had significantly higher levels of cytokines compared with controls, indicating that prior hyperglycemia can enhance the systemic inflammatory response to a moderate endotoxin dose, but that the maximum effects of endotoxin on production of inflammatory cytokines are not altered by transient high glucose exposure.
  
  
  CONCLUSIONS
  Systemic inflammation persists for a period following hyperglycemia, and this can enhance the systemic inflammatory response to a subsequent moderate stress.
authors.affiliation: Nutrition/Infection Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Pei-Ra
authors.initials: PR
authors.lastname: Ling
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Smith
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bistrian
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004731:Endotoxins / Q000633:toxicity*; D006943:Hyperglycemia / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004731:Endotoxins; C044101:endotoxin, Escherichia coli; D003345:Corticosterone