TY - JOUR

T1 - Arginine does not exacerbate markers of inflammation in cocultures of human enterocytes and leukocytes

AU - Parlesak, Alexandr

AU - Negrier, Isabelle

AU - Neveux, Nathalie

AU - Bode, Christiane

AU - Cynober, Luc

N1 - (Ekstern)

PY - 2007

Y1 - 2007

N2 - Enteral arginine supplementation in the critically ill has become a matter of controversy. In this study, we investigated effects of the addition of 0.4 and 1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte layer integrity, and amino acid transport. In this model, a monolayer of intestinal epithelial cells (Caco-2) separated compartments with nonpathogenic Escherichia coli and mononuclear leukocytes. Activation of enterocytes and leukocytes was assessed by the measurement of nitric oxide, TNF-α, IL-6, IL-8, IL-10, and IFN-γ. Further outcomes were the transepithelial flux of 22 amino acids, their catabolism, and the integrity of the enterocyte layer assessed as permeability of fluorescein dextran (M r 4400). Bacterial stimulation of intestinal epithelial cells enhanced the basolateral concentration of nitric oxide and all cytokines measured. Supplementation with arginine did not affect epithelial integrity, production of any of the cytokines investigated, or the amount of nitric oxide. The amino acid used primarily by nonstimulated intestinal epithelial cells cocultured with leukocytes was glutamine. Activation of IEC with bacteria significantly enhanced the catabolism of serine, asparagine, and lysine, and reduced glutamine catabolism. Addition of arginine increased ornithine formation and moderately reduced transepithelial transport of methionine and other amino acids. Hence, arginine supplementation does not interfere with inflammation-associated cross-talk between human enterocytes and leukocytes. Because it also does not seem to affect the integrity of enterocyte layers, a detrimental role of arginine during septic-like conditions seems unlikely.

AB - Enteral arginine supplementation in the critically ill has become a matter of controversy. In this study, we investigated effects of the addition of 0.4 and 1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte layer integrity, and amino acid transport. In this model, a monolayer of intestinal epithelial cells (Caco-2) separated compartments with nonpathogenic Escherichia coli and mononuclear leukocytes. Activation of enterocytes and leukocytes was assessed by the measurement of nitric oxide, TNF-α, IL-6, IL-8, IL-10, and IFN-γ. Further outcomes were the transepithelial flux of 22 amino acids, their catabolism, and the integrity of the enterocyte layer assessed as permeability of fluorescein dextran (M r 4400). Bacterial stimulation of intestinal epithelial cells enhanced the basolateral concentration of nitric oxide and all cytokines measured. Supplementation with arginine did not affect epithelial integrity, production of any of the cytokines investigated, or the amount of nitric oxide. The amino acid used primarily by nonstimulated intestinal epithelial cells cocultured with leukocytes was glutamine. Activation of IEC with bacteria significantly enhanced the catabolism of serine, asparagine, and lysine, and reduced glutamine catabolism. Addition of arginine increased ornithine formation and moderately reduced transepithelial transport of methionine and other amino acids. Hence, arginine supplementation does not interfere with inflammation-associated cross-talk between human enterocytes and leukocytes. Because it also does not seem to affect the integrity of enterocyte layers, a detrimental role of arginine during septic-like conditions seems unlikely.

U2 - 10.1093/jn/137.1.106

DO - 10.1093/jn/137.1.106

M3 - Journal article

C2 - 17182809

AN - SCOPUS:33846066733

VL - 137

SP - 106

EP - 111

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 1

ER -