• Efrossini Briassouli, Dimitris Goukos, George Daikos, Kleovoulos Apostolou, Christina Routsi, Serafim Nanas, and George Briassoulis.
• First Department of Internal Medicine, Medical School, University of Athens, Laikon Hospital, Athens, Greece.
• Nutrition. 2014 Oct 1;30(10):1185-94.

ObjectiveL-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.MethodsTime-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.ResultsIn 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.ConclusionHigh 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.Copyright © 2014 Elsevier Inc. All rights reserved.

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