title: Insulin increases the release of proinflammatory mediators.
abstract: BACKGROUND
  Strict glucose control with insulin is associated with decreased mortality in a mixed patient population in the intensive care unit. Controversy exists regarding the relative benefits of glucose control versus a direct advantageous effect of exogenous insulin. As a combined medical/surgical population differs significantly from the critically injured patient primed for secondary insult, our purpose was to determine the influence of insulin on activated macrophages. Our hypothesis was that insulin would directly abrogate the inflammatory cascade.
  
  
  METHODS
  Differentiated human monocytic THP-1 cells were stimulated with endotoxin (lipopolysaccharide [LPS], 100 ng/mL) for 6 hours. Cells were treated +/-10(-7) M insulin for 1 hour and 24 hours. Total RNA was isolated and gene expression for TNF-alpha and IL-6 performed using Q-RT-PCR. Supernatants were assayed for TNF-alpha and IL-6 protein by ELISA.
  
  
  RESULTS
  At 1 hour, compared with macrophages treated with LPS alone, macrophages treated with insulin produced significantly more TNF-alpha protein (11.4 +/- 5.9 pg/mL vs. 32.5 +/- 3.1 pg/mL; p < 0.03). At 24 hours compared with macrophages treated with LPS alone, macrophages treated with insulin produced significantly more TNF-alpha protein (83 +/- 2.02 pg/mL vs. 114 +/- 6.54 pg/mL; p < 0.01). However, gene expression of TNF-alpha and IL-6 was not different in LPS stimulated macrophages with and without insulin treatment at both 1 hour and 24 hours.
  
  
  CONCLUSIONS
  Contrary to our hypothesis, insulin does not have direct anti-inflammatory properties in this experimental model. In fact, insulin increases proinflammatory cytokine protein levels from activated macrophages.
authors.affiliation: Division of Trauma, Emergency and Critical Care Surgery, Department of Surgery, Stanford University Medical Center, Stanford, California 94305, USA. sbrundage@stanford.edu
authors.forename: Susan I
authors.initials: SI
authors.lastname: Brundage
authors.forename: Natalie N
authors.initials: NN
authors.lastname: Kirilcuk
authors.forename: Jason C
authors.initials: JC
authors.lastname: Lam
authors.forename: David A
authors.initials: DA
authors.lastname: Spain
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Zautke
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha