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Effect of l-Glutamine treatment on the expression of T and B cell surface molecules and secreted cytokines by cultured peripheral blood of healthy subjects

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Abstract

Background

l-Glutamine (l-GLN) is the most abundant amino acid in the human body. In hypercatabolic conditions, supplementation with l-GLN improves immunological function. Among the immune cells, the lymphocytes are the largest consumers of l-GLN in a catabolic disease state. Here, we evaluated the effect of l-GLN treatment on the expression of T and B cell surface molecules and secreted cytokines in cultured peripheral blood of healthy subjects.

Methods

Peripheral blood samples (N = 14) were cultured with or without l-GLN treatment and immunostained for T (anti-CD45, anti-CD3, anti-CD4, anti-CD8) and B (anti-CD19 and anti-CD20) lymphocytes at different time points over 24 h. In addition, secreted cytokines IL1-β, IL-6, IL-8, IL-10, IL-12p70, and TNF were measured at the same period with cytometric bead array.

Results

Our data showed that CD45 expression increased after 18 h in the l-GLN treatment group. On the other hand, l-GLN decreased the expression of total (CD3+) and helper (CD3+CD4+) T cells within 24 h, reducing the expression of cytotoxic cell markers (CD3+CD8+) at 12 and 18 h and of B cells (CD19+ and CD20+) at 18 h. Also, IL-1β and IL-10 cytokines increased at 18 and 24 h in the l-GLN treatment group supernatant of cultured peripheral blood.

Conclusions

The main finding of this study is that in vitro treatment with l-GLN can modulate the expression of T and B lymphocytes surface molecules and increase the secretion of IL-1β and IL-10 after 24 h.

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Data availability

Only if you give prior notice to the corresponding author. The datasets generated during and/or analyzed during the current study are available.

References

  1. Wilmore DW, Shabert JK. Role of glutamine in immunologic responses. Nutrition. 1998;14:618–26. https://doi.org/10.1016/S0899-9007(98)00009-4.

    Article  CAS  Google Scholar 

  2. Kao C, Hsu J, Bandi V, Jahoor F. Alterations in glutamine metabolism and its conversion to citrulline in sepsis. Am J Physiol Endocrinol Metab. 2013;304:E1359–64. https://doi.org/10.1152/ajpendo.00628.2012.

    Article  CAS  Google Scholar 

  3. Newsholme EA, Crabtree B, Ardawi MS. Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. Q J Exp Physiol. 1985;70:473–89.

    Article  CAS  Google Scholar 

  4. Cruzat VF, Petry ÉR, Tirapegui J. Glutamina: Aspectos bioquímicos, metabólicos, moleculares e suplementação. Rev Bras Med do Esporte. 2009;15:392–7. https://doi.org/10.1590/S1517-86922009000600015.

    Article  Google Scholar 

  5. Smedberg M, Grass NN, Pettersson L, et al. Plasma glutamine concentration after intensive care unit discharge: an observational study. Crit Care. 2014;18:1–8. https://doi.org/10.1186/s13054-014-0677-8.

    Article  Google Scholar 

  6. Berger MM, Binz PA, Roux C, et al.Exudative glutamine losses contribute to high needs after burn injury. J Parenter Enter Nutr. 2021;1–26.https://doi.org/10.1002/jpen.2227

  7. Matsuyama T, Yoshinaga SK, Shibue K, Mak TW. Comorbidity-associated glutamine deficiency is a predisposition to severe COVID-19. Cell Death Differ. 2021;28:3199–213. https://doi.org/10.1038/s41418-021-00892-y.

    Article  CAS  Google Scholar 

  8. Singer P, Blaser AR, Berger MM, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019;38:48–79. https://doi.org/10.1016/j.clnu.2018.08.037.

    Article  Google Scholar 

  9. Wischmeyer PE. The glutamine debate in surgery and critical care. Curr Opin Crit Care. 2019;25:322–8. https://doi.org/10.1097/MCC.0000000000000633.

    Article  Google Scholar 

  10. Papanikolopoulou A, Syrigos N, Vini L, et al. Use of oral glutamine in radiation-induced adverse effects in patients with thoracic and upper aerodigestive malignancies: Results of a prospective observational study. Oncol Lett. 2022;23. https://doi.org/10.3892/ol.2021.13137.

  11. Hörig H, Spagnoli GC, Filgueira L, et al. Exogenous glutamine requirement is confined to late events of T cell activation. J Cell Biochem. 1993;53:343–51.

    Article  Google Scholar 

  12. Chang WK, Yang KD, Chuang H, et al. Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Clin Immunol. 2002;104:151–60. https://doi.org/10.1006/clim.2002.5257.

    Article  CAS  Google Scholar 

  13. Lin MT, Kung SP, Yeh SL, et al. Glutamine-supplemented total parenteral nutrition attenuates plasma interleukin-6 in surgical patients with lower disease severity. World J Gastroenterol. 2005;11:6197–201.

    Article  CAS  Google Scholar 

  14. Fan J, Wu L, Li G, et al. Effects of enteral nutrition with parenteral glutamine supplementation on the immunological function in septic rats. Br J Nutr. 2015;113:1712–22. https://doi.org/10.1017/S0007114515001099.

    Article  CAS  Google Scholar 

  15. Jordan I, Balaguer M, Esteban ME, et al. Glutamine effects on heat shock protein 70 and interleukines 6 and 10: randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children. Clin Nutr. 2016;35:34–40. https://doi.org/10.1016/j.clnu.2015.01.019.

    Article  CAS  Google Scholar 

  16. Marino LV, Pathan N, Meyer RW, et al. An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators. Nutrition. 2016;32:375–83. https://doi.org/10.1016/j.nut.2015.09.007.

    Article  CAS  Google Scholar 

  17. Huang J, Liu J, Chang G, et al. Glutamine supplementation attenuates the inflammation caused by LPS-induced acute lung injury in mice by regulating the TLR4/MAPK signaling pathway. Inflammation. 2021;44:2180–92. https://doi.org/10.1007/s10753-021-01491-2.

    Article  CAS  Google Scholar 

  18. Mohajeri M, Horriatkhah E, Mohajery R. The effect of glutamine supplementation on serum levels of some inflammatory factors, oxidative stress, and appetite in COVID-19 patients: a case–control study. Inflammopharmacology. 2021;29:1769–76. https://doi.org/10.1007/s10787-021-00881-0.

    Article  CAS  Google Scholar 

  19. Arribas-lópez E, Omorogieva O, Zand N, et al. A meta-analysis of the effect on wound healing of amino acids arginine and glutamine. Nutrients. 2021;13:2498.

  20. Peng X, Yan H, You Z, et al. Glutamine granule-supplemented enteral nutrition maintains immunological function in severely burned patients. Burns. 2006;32:589–93. https://doi.org/10.1016/j.burns.2005.11.020.

    Article  Google Scholar 

  21. Newsholme P, Curi R, PithonCuri TC, et al. Glutamine metabolism by lymphocytes, macrophages, and neutrophils: its importance in health and disease. J Nutr Biochem. 1999;10:316–24. https://doi.org/10.1016/S0955-2863(99)00022-4.

    Article  CAS  Google Scholar 

  22. Santos LA, dos Silvério A, SD, ORFÃO LH,. Perfil leucocitário de uma população do sul de minas gerais. Rev da Univ Val do Rio Verde. 2015;13:506–13.

    Google Scholar 

  23. Rosenfeld LG, Malta DC, Szwarcwald CL, et al. Reference values for blood count laboratory tests in the Brazilian adult population, national health survey. Rev Bras Epidemiol. 2019;22:1–13. https://doi.org/10.1590/1980-549720190003.supl.2.

    Article  Google Scholar 

  24. Hou YC, Wu JM, Wang MY, et al. Glutamine supplementation attenuates expressions of adhesion molecules and chemokine receptors on t cells in a murine model of acute colitis. Mediators Inflamm. 2014. https://doi.org/10.1155/2014/837107.

    Article  Google Scholar 

  25. Hu YM, Hsiung YC, Pai MH, Yeh SL. Glutamine administration in early or late septic phase downregulates lymphocyte PD-1/PD-L1 expression and the inflammatory response in mice with polymicrobial sepsis. J Parenter Enter Nutr. 2018;42:538–49. https://doi.org/10.1177/0148607117695245.

    Article  CAS  Google Scholar 

  26. Cetinbas F, Yelken B, Gulbas Z. Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome. J Crit Care. 2010. https://doi.org/10.1016/j.jcrc.2010.03.011.

    Article  Google Scholar 

  27. Wells SM, Kew S, Yaqoob P, et al. Dietary glutamine enhances cytokine production by murine macrophages. Nutrition. 1999;15:881–4. https://doi.org/10.1016/S0899-9007(99)00184-7.

    Article  CAS  Google Scholar 

  28. Yaqoob P, Calder PC. Cytokine production by human peripheral blood mononuclear cells: differential senstivity to glutamine availability. Cytokine. 1998;10:790–4. https://doi.org/10.1006/cyto.1998.0358.

    Article  CAS  Google Scholar 

  29. Raizel R, Leite JSM, Hypólito TM, et al. Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise. Br J Nutr. 2016;116:470–9. https://doi.org/10.1017/S0007114516001999.

    Article  CAS  Google Scholar 

  30. Porsani MYH, Paludetti M, Orlando DR, et al. Protective effect of β-glucan and glutamine on intestinal and immunological damage in mice induced by cytarabine (Ara-C). Pesqui Vet Bras. 2017;37:977–83. https://doi.org/10.1590/s0100-736x2017000900013.

    Article  Google Scholar 

  31. Safi S, Batumalaie K, Mansor M, et al. Glutamine treatment attenuates hyperglycemia-induced mitochondrial stress and apoptosis in umbilical vein endothelial cells. Clinics. 2015;70:569–76. https://doi.org/10.6061/clinics/2015(08)07.

    Article  Google Scholar 

  32. Chang WK, Yang KD, Shaio MF. Lymphocyte proliferation modulated by glutamine: involved in the endogenous redox reaction. Clin Exp Immunol. 1999. https://doi.org/10.1046/j.1365-2249.1999.01009.x.

    Article  Google Scholar 

  33. Cruzat V, Rogero MM, Keane KN, et al. Glutamine: metabolism and immune function, supplementation and clinical translation. 2018;1–31. https://doi.org/10.3390/nu10111564

  34. Janský L, Reymanová P, Kopecký J. Dynamics of cytokine production in human peripheral blood mononuclear cells stimulated by LPS or infected by Borrelia. 2003;593–598

  35. Nunes A, Koterba E, Alves V, et al. Terapia Nutricional no Paciente Grave. Proj Diretrizes. 2011;1–13.

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Funding

This study was funded by the Laboratory of Immunology and Molecular Biology-Federal University of Bahia and enteral and Parenteral Nutrition Service of Hospital Santa Izabel-BA. NEVES-AMORIM, EG; SANTOS, S. Q and ARAÚJO-PEREIRA, M received Research grants the Federal University of Bahia.

Author information

Authors and Affiliations

  1. Laboratory of Immunology and Molecular Biology, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil

    E. G. Neves-Amorim, S. Q. Santos, M. Araújo-Pereira, Z. V. B. Santana, E. K. S. Bomfim, N. M. B. L. Chagas, R. R. Conceição, M. D. M. Freire, A. J. L. Torres, V. Fortuna, J. R. Meyer & S. M. Freire

  2. Department of Biomorphology, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil

    A. J. L. Torres

  3. Department of Biochemistry and Biophysics, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil

    V. Fortuna

  4. Department of Biotechnology, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil

    G. C. de Carvalho & S. M. Freire

  5. Department of Bio-Interaction, Health Sciences Institute, Federal University of Bahia, Salvador, Brazil

    J. R. Meyer

  6. School of Medicine, Department of Surgery, Federal University of Bahia, Salvador, Brazil

    A. N. M. Freire

  7. Enteral and Parenteral Nutrition Service, Santa Izabel Hospital, Santa Casa de Misericórdia da Bahia, Salvador, Brazil

    A. N. M. Freire

Authors
  1. E. G. Neves-Amorim
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  2. S. Q. Santos
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  3. M. Araújo-Pereira
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  4. Z. V. B. Santana
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  5. E. K. S. Bomfim
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  6. N. M. B. L. Chagas
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  7. R. R. Conceição
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  8. M. D. M. Freire
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  9. A. J. L. Torres
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  10. V. Fortuna
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  11. G. C. de Carvalho
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  12. J. R. Meyer
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  13. S. M. Freire
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  14. A. N. M. Freire
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Contributions

Neves-Amorim, E. G.: formal analysis, investigation, writing-original draft; Santos, S. Q.: investigation; Araújo-Pereira, M.: investigation; Santana, Z. V. B.: investigation; Bomfim, E. K. S: investigation; Chagas, N. M. B. L.: investigation; Conceição, R. R.: investigation; Freire, M. D. M.: general analyses, review and editing; Torres, A. J. L.: formal analysis, conceptualization, writing-review and editing; Fortuna, V.: formal analysis, conceptualization, writing-review and editing; Carvalho, G. C.: formal analysis, conceptualization, writing-review and editing; Meyer, J. R.: conceptualization, resources; Freire, S. M.: conceptualization, methodology, supervision, project administration, resources, funding acquisition, writing-review and editing; Freire, A. N. M.: conceptualization, methodology, project administration, funding acquisition, resources.

Corresponding author

Correspondence to E. G. Neves-Amorim.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The institutional review board of the Bahiana School of Medicine and Public Health (CAAE:57274316.3.0000.5544) approved this study.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no competing interests.

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Neves-Amorim, E.G., Santos, S.Q., Araújo-Pereira, M. et al. Effect of l-Glutamine treatment on the expression of T and B cell surface molecules and secreted cytokines by cultured peripheral blood of healthy subjects. Nutrire 47, 19 (2022). https://doi.org/10.1186/s41110-022-00169-5

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