Glutamine suppresses Hsp72 not Hsp90α and is not inducing Th1, Th2, or Th17 cytokine responses in human septic PBMCs

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 30; no. 10; pp. 1185 - 1194
• Main Authors: Briassouli, Efrossini, M.D, Goukos, Dimitris, M.S, Daikos, George, M.D., Ph.D, Apostolou, Kleovoulos, M.D, Routsi, Christina, M.D., Ph.D, Nanas, Serafim, M.D., Ph.D, Briassoulis, George, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2014
• Subjects: Cytokines; Cytokines - metabolism; Dipeptides - pharmacology; Gastroenterology and Hepatology; Glutamine; Glutamine - pharmacology; Heat shock protein 72; Heat shock protein 90α; Heat-Shock Proteins - antagonists & inhibitors; HSP72 Heat-Shock Proteins - antagonists & inhibitors; Humans; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lipopolysaccharide; Lipopolysaccharides; Peripheral blood mononuclear cells; Sepsis - immunology; Severe sepsis; Th1 Cells - metabolism; Th17 Cells - metabolism; Th2 Cells - metabolism; Cytokines; Severe sepsis; Lipopolysaccharide; Peripheral blood mononuclear cells; Heat shock protein 72; Heat shock protein 90α; Glutamine
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2014.01.018

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. Conclusion 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.