title: Intravenous Glutamine Administration Modulates TNF-α/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model.
abstract: Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN. Two-month-old male Balb/c mice were subjected to a low-protein diet (2 % protein) and stimulated intravenously with LPS 1 h prior to the injection of 0.75 mg/kg GLN. Malnourished animals showed a reduced number of total peritoneal cells. Malnourished animals stimulated with LPS or LPS plus GLN did not show differences in peritoneal cell counts; however, the control group showed increased cellularity after LPS stimulus, which was reversed after GLN injection. Further, in the animals from both groups stimulated with LPS, GLN decreased the circulating levels of TNF-α and the levels of TNF-α produced by peritoneal cells; additionally, GLN decreased the IL-10 circulating levels in the malnourished animals stimulated with LPS. In addition, peritoneal cells of the control and malnourished groups stimulated with LPS showed a negative modulation of the NFkB signaling pathway after GLN injection. In conclusion, this study shows that GLN has the capacity to reduce TNF-α synthesis as well as to act as a negative regulator of NFkB phosphorylation, leading to a positive outcome in the control of TNF-α production.
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, 05508-000, Brazil.
authors: Andressa Cristina Antunes
authors: AC
authors: Santos
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, 05508-000, Brazil.
authors: Carolina Argondizo
authors: CA
authors: Correia
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, 05508-000, Brazil.
authors: Dalila Cunha
authors: DC
authors: de Oliveira
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, 05508-000, Brazil.
authors: Amanda
authors: A
authors: Nogueira-Pedro
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, 05508-000, Brazil.
authors: Primavera
authors: P
authors: Borelli
authors: Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, São Paulo, 05508-000, Brazil. hemato@usp.br.
authors: Ricardo Ambrosio
authors: RA
authors: Fock
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005973:Glutamine / Q000008:administration & dosage* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D011502:Protein-Energy Malnutrition / Q000188:drug therapy / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D016753:Interleukin-10
keywords: glutamine; lps; macrophages; protein malnutrition; tnf-α and nfkB