, Volume 68, Issue 5, pp 1949–1961 | Cite as

Effects of free amino acids on cytokine secretion and proliferative activity of feline T cells in an in vitro study using the cell line MYA-1

  • Nadine Paßlack
  • Marcus G. Doherr
  • Jürgen Zentek
Original Article


In vitro studies might be an interesting screening method for targeted in vivo studies in the field of immunonutrition and help to reduce and refine animal studies. As the role of amino acids for immune function of cats has not been evaluated in detail so far, the present study aimed at investigating the effects of eight different amino acids (arginine, leucine, isoleucine, valine, glutamine, lysine, threonine and tryptophan) in six concentrations each (0, 0.25, 0.5, 1, 2 and 8x the cat blood level) on cytokine secretion and proliferative activity of feline T cells (MYA-1) in vitro. The results demonstrated that high doses of arginine increased IL-4, IL-10 and TNF-α secretion of T cells, while increasing concentrations of lysine increased IL-10 secretion and proliferative activity of the T cells. High doses of leucine enhanced GM-CSF and IL-10 secretion, while concentrations of threonine in the cell culture media greater than blood concentration also increased GM-CSF and additionally TNF-α secretion of the cells. The effects of glutamine and isoleucine on T cell function were only small. In conclusion, the present in vitro study could evaluate the immunomodulating potential of specific amino acids for feline T cell function. High doses of arginine, lysine, leucine and threonine had a significant impact on cytokine secretion and proliferative activity of the T cells. Targeted in vivo studies should investigate the clinical relevance of dietary supplementation of those amino acids in healthy and diseased cats as a next step.


Feline T cells Amino acids Cytokines Proliferative activity In vitro 



This study was funded by the ESVCN/WALTHAM™ Research Grant 2012. The authors are grateful to Petra Huck for support in laboratory work.


  1. Alazawy A, Arshad SS, Bejo MH, Omar AR, Tengku Ibrahim TA, Sharif S, Bande F, Awang-Isa K (2011) Ultrastructure of Felis catus whole fetus (Fcwf-4) cell culture following infection with feline coronavirus. J Electron Microsc (Tokyo) 60:275–282CrossRefGoogle Scholar
  2. Boenzli E, Robert-Tissot C, Sabatino G, Cattori V, Meli ML, Gutte B, Rovero P, Flynn N, Hofmann-Lehmann R, Lutz H (2011) In vitro inhibition of feline leukaemia virus infection by synthetic peptides derived from the transmembrane domain. Antivir Ther 16:905–913CrossRefGoogle Scholar
  3. Bogdan C (2001) Nitric oxide and the immune response. Nat Immunol 2:907–916CrossRefGoogle Scholar
  4. Bol S, Bunnik EM (2015) Lysine supplementation is not effective for the prevention or treatment of feline herpesvirus 1 infection in cats: a systematic review. BMC Vet Res 11:284CrossRefGoogle Scholar
  5. Bonham M, O’Connor JM, Hannigan BM, Strain JJ (2002) The immune system as a physiological indicator of marginal copper status? Br J Nutr 87:393–403CrossRefGoogle Scholar
  6. Chew BP (1993) Role of carotenoids in the immune response. J Dairy Sci 76:2804–2811CrossRefGoogle Scholar
  7. Chew BP (1995) Antioxidant vitamins affect food animal immunity and health. J Nutr 125:1804S–1808SGoogle Scholar
  8. De Vrese M, Schrezenmeir J (2008) Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 111:1–66Google Scholar
  9. Drazenovich TL, Fascetti AJ, Westermeyer HD, Sykes JE, Bannasch MJ, Kass PH, Hurley KF, Maggs DJ (2009) Effects of dietary lysine supplementation on upper respiratory and ocular disease and detection of infectious organisms in cats within an animal shelter. Am J Vet Res 70:1391–1400CrossRefGoogle Scholar
  10. Fraker PJ, King LE (2004) Reprogramming of the immune system during zinc deficiency. Ann Rev Nutr 24:277–298CrossRefGoogle Scholar
  11. Heinze CR, Larsen JA, Kass PH, Fascetti AJ (2009) Plasma amino acid and whole blood taurine concentrations in cats eating commercially prepared diets. Am J Vet Res 70:1374–1382CrossRefGoogle Scholar
  12. Ibs KH, Rink L (2003) Zinc-altered immune function. J Nutr 133:1452S–14556SGoogle Scholar
  13. Klotz LO, Kroencke KD, Buchczyk DP, Sies H (2003) Role of copper, zinc, selenium, and tellurium in the cellular defense against oxidative and nitrosative stress. J Nutr 133:1448S–1451SGoogle Scholar
  14. Li P, Yin Y-L, Li D, Kim SW, Wu G (2007) Amino acids and immune function. Br J Nutr 98:237–252CrossRefGoogle Scholar
  15. Maggs DJ, Nasisse MP, Kass PH (2003) Efficacy of oral supplementation with l-lysine in cats latently infected with feline herpesvirus. Am J Vet Res 64:37–42CrossRefGoogle Scholar
  16. Maggs DJ, Sykes JE, Clarke HE, Yoo SH, Kass PH, Lappin MR, Rogers QR, Waldron MK, Fascetti AJ (2006) Effects of dietary lysine supplementation in cats with enzootic upper respiratory disease. J Feline Med Surg 9:97–108CrossRefGoogle Scholar
  17. Martin CK, Dirksen WP, Shu ST, Werbeck JL, Thudi NK, Yamaguchi M, Wolfe TD, Heller KN, Rosol TJ (2011) Characterization of bone resorption in novel in vitro and in vivo models of oral squamous cell carcinoma. Oral Oncol 48:491–499CrossRefGoogle Scholar
  18. Mayne ST (1996) Beta-carotene, carotenoids and disease prevention in human. FASEB J 10:690–701Google Scholar
  19. Mochizuki H, Takahashi M, Nishigaki K, Ide T, Goto-Koshino Y, Watanabe S, Sato H, Sato M, Kotera Y, Fujino Y, Ohno K, Uchida K, Tsujimoto H (2011) Establishment of a novel feline leukemia virus (FeLV)-negative B-cell cell line from a cat with B-cell lymphoma. Vet Immunol Immunopathol 140:307–311CrossRefGoogle Scholar
  20. National Research Council (NRC) (2006) Nutrient requirements of dogs and cats. The National Academies Press, WashingtonGoogle Scholar
  21. Percival SS (1998) Copper and immunity. Am J Clin Nutr 67:1064S–1085SGoogle Scholar
  22. Raber P, Ochoa AC, Rodríguez PC (2012) Metabolism of l-arginine by myeloid-derived suppressor cells in cancer: mechanisms of T cell suppression and therapeutic perspectives. Immunol Invest 41:614–634CrossRefGoogle Scholar
  23. Ramesh HP, Yamaki K, Tsushida T (2002) Effect of fenugreek (Trigonella foenum-graecum L.) galactomannan fractions on phagocytosis in rat macrophages and on proliferation and IgM secretion in HB4C5 cells. Carbohydr Polym 50:79–83CrossRefGoogle Scholar
  24. Rees TM, Lubinski JL (2008) Oral supplementation with l-lysine did not prevent upper respiratory infection in a shelter population of cats. J Feline Med Surg 10:510–513CrossRefGoogle Scholar
  25. Robert-Tissot C, Rüegger VL, Cattori V, Meli ML, Riond B, Gomes-Keller MA, Vögtlin A, Wittig B, Juhls C, Hofmann-Lehmann R, Lutz H (2011) The innate antiviral immune system of the cat: molecular tools for the measurement of its state of activation. Vet Immunol Immunopathol 143:269–281CrossRefGoogle Scholar
  26. Roth E (2008) Nonnutritive effects of glutamine. J Nutr 138:2025S–2031SGoogle Scholar
  27. Rutherfurd-Markwick KJ, Hendriks WH, Morel PC, Thomas DG (2013) The potential for enhancement of immunity in cats by dietary supplementation. Vet Immunol Immunopathol 152:333–340CrossRefGoogle Scholar
  28. Satyaraj E (2011) Emerging paradigms in immunonutrition. Top Companion Anim Med 26:25–32CrossRefGoogle Scholar
  29. Shimada D, Fukuda A, Kanouchi H, Matsumoto M, Oka T (2006) Vitamin B6 suppresses growth of the feline mammary tumor cell line FRM. Biosci Biotechnol Biochem 70:1038–1040CrossRefGoogle Scholar
  30. Sikalidis AK (2015) Amino acids and immune response: a role for cysteine, glutamine, phenylalanine, tryptophan and arginine in T-cell function and cancer? Pathol Oncol Res 21:9–17CrossRefGoogle Scholar
  31. Stiles J, Townsend WM, Rogers QR, Krohne SG (2002) Effect of oral administration of l-lysine on conjunctivitis caused by feline herpesvirus in cats. Am J Vet Res 63:99–103CrossRefGoogle Scholar
  32. Turner MD, Nedjai B, Hurst T, Pennington DJ (2014) Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 1843:2563–2582CrossRefGoogle Scholar
  33. Webb AL, Villamor E (2007) Update: effects of antioxidant and non-antioxidant vitamin supplementation on immune function. Nutr Rev 65:181–217CrossRefGoogle Scholar
  34. Wintergerst ES, Maggini S, Hornig DH (2006) Immune-enhancing role of Vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab 50:85–94CrossRefGoogle Scholar
  35. Wintergerst ES, Maggini S, Hornig DH (2007) Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab 51:301–323CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Nadine Paßlack
    • 1
  • Marcus G. Doherr
    • 2
  • Jürgen Zentek
    • 1
  1. 1.Department of Veterinary Medicine, Institute of Animal NutritionFreie Universität BerlinBerlinGermany
  2. 2.Department of Veterinary Medicine, Institute of Veterinary Epidemiology and BiostatisticsFreie Universität BerlinBerlinGermany

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