, Volume 39, Issue 6, pp 1883–1891 | Cite as

Intravenous Glutamine Administration Modulates TNF-α/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model

  • Andressa Cristina Antunes Santos
  • Carolina Argondizo Correia
  • Dalila Cunha de Oliveira
  • Amanda Nogueira-Pedro
  • Primavera Borelli
  • Ricardo Ambrosio Fock


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.


protein malnutrition macrophages lps glutamine tnf-α and nfkB 



This investigation was supported by grants from the Fundação de Amparo a Pesquisa do Estado de São Paulo—FAPESP (2014/06872-2).

Compliance with ethical standards

This study was approved by the ethics committee of the School of Pharmaceutical Sciences at the University of São Paulo (protocol number CEUA/FCF/ 394).


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Andressa Cristina Antunes Santos
    • 1
  • Carolina Argondizo Correia
    • 1
  • Dalila Cunha de Oliveira
    • 1
  • Amanda Nogueira-Pedro
    • 1
  • Primavera Borelli
    • 1
  • Ricardo Ambrosio Fock
    • 1
  1. 1.Department of Clinical and Toxicological Analysis, School of Pharmaceutical SciencesUniversity of Sao PauloSão PauloBrazil

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