title: Glutamine suppresses Hsp72 not Hsp90α and is not inducing Th1, Th2, or Th17 cytokine responses in human septic PBMCs.
abstract: OBJECTIVE
  L-Alanyl-glutamine (L-Ala-Gln) is a pharmaco-nutrient commonly used in nutrition regimens due to its immunomodulatory effects. In critically ill patients who are septic, L-Ala-Gln was associated with an increase in mortality. The aim of this study was to investigate whether L-Ala-Gln modulated heat shock protein (Hsp)-72, 90-α, T helper (Th)1, Th2, and Th17 cytokine expression in the peripheral blood mononuclear cells (PBMC) of patients with severe sepsis.
  
  
  METHODS
  Time-dose effects of L-Ala-Gln were compared with those of L-glutamine (L-Gln) and lipopolysaccharide (LPS) and to healthy controls. PBMCs were incubated with 1 or 10 μg/mL LPS, 5 or 10 mM L-Gln, and 5 or 10 mM L-Ala-Gln for different periods of time (0; 4; 24 h) when culture supernatants were harvested.
  
  
  RESULTS
  In both groups, basal Hsp72 increased over time (P < 0.02); Hsp90-α levels declined in controls (P < 0.02) but remained increased in septic patients (P < 0.02), not exhibiting any significant time-response trend. Both Glns suppressed Hsp72 in septic and controls at 10 mM by 4 h (P < 0.045) and Hsp90-α in the control group by 24 h (P < 0.045). LPS did not induce Hsps in either group. L-Ala-Gln did not induce any of the Th1, Th2, and Th17 cytokines in either group.
  
  
  CONCLUSIONS
  High doses of L-Gln or L-Ala-Gln do not induce any of the Th1, Th2, and Th17 cytokines in either healthy or septic human PBMCs. High Gln doses suppress Hsp72 in septic and control PBMCs. Hsp90-α time-series expression declines, contrasting the increasing trend of Hsp72 in healthy controls. Hsp90-α sustains increased levels in septic supernatants, showing a characteristic longitudinal behavior needed further elucidation.
authors: First Department of Internal Medicine, Medical School, University of Athens, Laikon Hospital, Athens, Greece.
authors: Efrossini
authors: E
authors: Briassouli
authors: First Department of Internal Medicine, Medical School, University of Athens, Laikon Hospital, Athens, Greece.
authors: Dimitris
authors: D
authors: Goukos
authors: First Department of Internal Medicine, Medical School, University of Athens, Laikon Hospital, Athens, Greece.
authors: George
authors: G
authors: Daikos
authors: First Department of Critical Care, Medical School, University of Athens, Evangelismos Hospital, Athens, Greece.
authors: Kleovoulos
authors: K
authors: Apostolou
authors: First Department of Critical Care, Medical School, University of Athens, Evangelismos Hospital, Athens, Greece.
authors: Christina
authors: C
authors: Routsi
authors: First Department of Critical Care, Medical School, University of Athens, Evangelismos Hospital, Athens, Greece.
authors: Serafim
authors: S
authors: Nanas
authors: Pediatric Intensive Care Unit, University Hospital, University of Crete, Heraklion, Greece. Electronic address: Ggbriass@otenet.gr.
authors: George
authors: G
authors: Briassoulis
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D018805:Sepsis / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D016207:Cytokines; D004151:Dipeptides; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D005973:Glutamine; C054122:alanylglutamine
keywords: Cytokines; Glutamine; Heat shock protein 72; Heat shock protein 90α; Lipopolysaccharide; Peripheral blood mononuclear cells; Severe sepsis