Amino acid and dipeptide combination strongly attenuates endotoxemic cytokine production in human whole-blood monocytes

Christoph Raspé,¹ Elke Czeslick,² Anja Leimert,¹ Tanja Rossberg,³ Brit Hofmann,⁴ Andreas Simm,⁴ Arved Weimann,⁵ Armin Sablotzki<sup>2

1</sup>Department of Anesthesiology and Critical Care Medicine, Halle-Wittenberg University, Halle, ²Department of Anesthesiology, Critical Care and Pain Therapy, ³Department of Otorhinolaryngology, St Georg Medical Center, Leipzig, ⁴Department of Cardiac and Thoracic Surgery, Halle-Wittenberg University, Halle, ⁵Department of Abdominal and Visceral Surgery, St Georg Medical Center, Leipzig, Germany

Objective: The study reported here aimed to analyze the anti-inflammatory and immunmodulatory impact of arginine, glycine, glutamine, and the combination of these amino acids on the intracellular expression of proinflammatory cytokines during sepsis. These amino acids were tested on lipopolysaccharide (LPS)-stimulated human monocytes in a whole-blood system and examined using flow cytometry.
Materials and methods: The whole blood of twelve healthy volunteers processed immediately after withdrawal was incubated with arginine (2 and 5 mM), glycine (2 and 5 mM), glycyl-glutamine (2 and 5 mM), and the amino acid and dipeptide solution Glamin^® (Fresenius Kabi, Bad Homburg, Germany) at three concentrations (5%, 10%, 20%), with or without LPS (0.2 ng/mL) stimulation. Cytokine-producing monocytes were phenotyped in whole blood and the intracellular expression of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α was assessed by flow cytometry.
Results: In whole-blood samples from volunteers, used to best imitate physiological cellular interactions, the amino acid and dipeptide solution Glamin, containing arginine, glycine, glycyl-glutamine, was able to significantly and dose-dependently diminish LPS-induced production of proinflammatory cytokines such as IL-6, IL-8, and TNF-α in human monocytes. However, single incubation with the amino acids arginine, glycine, and glycyl-glutamine individually did not affect alterations in the expression of IL-6, IL-8, or TNF-α.
Conclusion: The amino acid and dipeptide solution Glamin, composed of glycine, arginine, and glycyl-glutamine, had strong anti-inflammatory and immunomodulatory effects during the induced experimental sepsis, as it significantly downregulated intracellular expression of proinflammatory cytokines in human whole-blood monocytes. However, only incubation with a combination of amino acids (ie, Glamin), rather than individual amino acids, demonstrated an inhibitory impact on cytokine production in LPS-stimulated monocytes. The results indicate that a combination of amino acids may potentiate the anti-inflammatory response, leading to a marked suppression of TNF-α, IL-6, and IL-8 during sepsis.

Keywords: sepsis, anti-inflammatory response, glycine, arginine, glycyl-glutamine, Glamin^®