Article ID Journal Published Year Pages File Type
5897871 Cytokine 2013 6 Pages PDF
Abstract

To investigate the effects of the commonly-used immunomodulators l-glutamine, l-alanine, and the combination of both l-alanyl-l-glutamine (Dipeptamin®) on intracellular expression of IL-6, IL-8, and TNF-α during endotoxemia, lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system were investigated by flow cytometry.Whole blood of twenty-seven healthy volunteers was stimulated with LPS and incubated with three different amino acid solutions (1. l-glutamine, 2. l-alanine, 3. l-alanyl-l-glutamine, each concentration 2 mM, 5 mM, incubation time 3 h). CD14+ monocytes were phenotyped in whole-blood and intracellular expression of cytokines was assessed by flow cytometry.Our investigations showed for the first time in whole blood probes, imitating best physiologically present cellular interactions, that l-glutamine caused a dose-independent inhibitory effect on IL-6 and TNF-α production in human monocytes stimulated with LPS. However, l-alanine had contrary effects on IL-6 expression, significantly upregulating expression of IL-6 in LPS-treated monocytes. The impact of l-alanine on the expression of TNF-α was comparable with glutamine. Neither amino acid was able to affect IL-8 production in LPS-stimulated monocytes. The combination of both did not influence significantly IL-6 and IL-8 expression in monocytes during endotoxemia, however strongly reduced TNF-α production.For the regulation of TNF-α, l-glutamine, l-alanine and the combination of both show a congruent and exponentiated downregulating effect during endotoxemia, for the modulation of IL-6, l-glutamine and l-alanine featured opposite regulation leading to a canceling impact of each other when recombining both amino acids.

► Glutamine showed an inhibitory effects on TNF-α and IL-6 in LPS-stimulated human monocytes. ► Alanine had contrary effects on IL-6 and comparable impact on TNF-α in septic monocytes. ► Using flow cytometry neither amino acid affected IL-8 production in septic human monocytes. ► By combining glutamine and alanine, the inhibitory effect on TNF-α was enhanced. ► The suppressing impact of glutamine on IL-6 by additionally disposed alanine was attenuated.

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