DOI QR코드

DOI QR Code

Agrobacterium sp.-derived β-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study

  • Lee, Yeon Joo (Department of Food and Nutrition, Hanyang University) ;
  • Paik, Doo-Jin (Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Kwon, Dae Young (Devision of Strategic Food Research, Korea Food Research Institute) ;
  • Yang, Hye Jeong (Devision of Strategic Food Research, Korea Food Research Institute) ;
  • Park, Yongsoon (Department of Food and Nutrition, Hanyang University)
  • Received : 2016.06.29
  • Accepted : 2016.11.22
  • Published : 2017.02.01

Abstract

BACKGROUND/OBJECTIVES: The present study investigated the hypothesis that a highly pure linear ${\beta}$-1,3-glucan produced by Agrobacterium sp. R259 enhances human natural killer (NK) cell activity and suppresses pro-inflammatory cytokines. SUBJECTS/METHODS: In an eight-week, double-blind, randomized, placebo-controlled clinical trial, 83 healthy adults with white blood cell counts of $4,000-8,000cells/{\mu}L$ were participated and randomly assigned to take two capsules per day containing either 350 mg ${\beta}$-1,3-glucan or placebo. Six participants withdrew their study consent or were excluded due to NK cell activity levels outside the normal range. NK cell activity and serum levels of immunoglobulin G (IgG) and cytokines, such as interferon (IFN)-${\gamma}$, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-${\alpha}$ were measured. RESULTS: NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the ${\beta}$-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of ${\beta}$-1,3-glucan also significantly increased NK cell activity compared with placebo after adjusting for smoking and stress status (P = 0.009). In particular, the effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration ${\beta}$-1,3-glucan did not significantly modulate the levels of IFN-${\gamma}$, IL-2, IL-4, IL-6, IL-12, TNF-${\alpha}$ and IgG compared with the placebo. CONCLUSION: The results showed that supplementation with bacterial ${\beta}$-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.

Keywords

References

  1. Chan GC, Chan WK, Sze DM. The effects of ${\beta}$-glucan on human immune and cancer cells. J Hematol Oncol 2009;2:25. https://doi.org/10.1186/1756-8722-2-25
  2. Murphy EA, Davis JM, Carmichael MD. Immune modulating effects of ${\beta}$-glucan. Curr Opin Clin Nutr Metab Care 2010;13:656-61. https://doi.org/10.1097/MCO.0b013e32833f1afb
  3. Willment JA, Marshall AS, Reid DM, Williams DL, Wong SY, Gordon S, Brown GD. The human ${\beta}$-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. Eur J Immunol 2005;35:1539-47. https://doi.org/10.1002/eji.200425725
  4. Mantovani MS, Bellini MF, Angeli JP, Oliveira RJ, Silva AF, Ribeiro LR. ${\beta}$-glucans in promoting health: prevention against mutation and cancer. Mutat Res 2008;658:154-61. https://doi.org/10.1016/j.mrrev.2007.07.002
  5. Yoon TJ, Koppula S, Lee KH. The effects of ${\beta}$-glucans on cancer metastasis. Anticancer Agents Med Chem 2013;13:699-708. https://doi.org/10.2174/1871520611313050004
  6. Heinsbroek SE, Williams DL, Welting O, Meijer SL, Gordon S, de Jonge WJ. Orally delivered ${\beta}$-glucans aggravate dextran sulfate sodium (DSS)-induced intestinal inflammation. Nutr Res 2015;35:1106-12. https://doi.org/10.1016/j.nutres.2015.09.017
  7. Kohl A, Gogebakan O, Mohlig M, Osterhoff M, Isken F, Pfeiffer AF, Weickert MO. Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-${\beta}$-glycan consumption in overweight humans. Nutr Res 2009;29:248-54. https://doi.org/10.1016/j.nutres.2009.03.002
  8. Nameda S, Harada T, Miura NN, Adachi Y, Yadomae T, Nakajima M, Ohno N. Enhanced cytokine synthesis of leukocytes by a ${\beta}$-glucan preparation, SCG, extracted from a medicinal mushroom, Sparassis crispa. Immunopharmacol Immunotoxicol 2003;25:321-35. https://doi.org/10.1081/IPH-120024500
  9. Bergendiova K, Tibenska E, Majtan J. Pleuran (${\beta}$-glucan from Pleurotus ostreatus) supplementation, cellular immune response and respiratory tract infections in athletes. Eur J Appl Physiol 2011;111:2033-40. https://doi.org/10.1007/s00421-011-1837-z
  10. Eom SY, Zhang YW, Kim NS, Kang JW, Hahn YS, Shin KS, Song HG, Park SY, Kim JS, Kim H, Kim YD. Effects of Keumsa Sangwhang (Phellinus linteus) mushroom extracts on the natural killer cell activity in human. Korean J Food Sci Technol 2006;38:717-9.
  11. Nieman DC, Henson DA, McMahon M, Wrieden JL, Davis JM, Murphy EA, Gross SJ, McAnulty LS, Dumke CL. ${\beta}$-glucan, immune function, and upper respiratory tract infections in athletes. Med Sci Sports Exerc 2008;40:1463-71. https://doi.org/10.1249/MSS.0b013e31817057c2
  12. Smiderle FR, Baggio CH, Borato DG, Santana-Filho AP, Sassaki GL, Iacomini M, Van Griensven LJ. Anti-inflammatory properties of the medicinal mushroom Cordyceps militaris might be related to its linear (13)-${\beta}$-D-glucan. PLoS One 2014;9:e110266. https://doi.org/10.1371/journal.pone.0110266
  13. Kim MK, Ryu KE, Choi WA, Rhee YH, Lee IY. Enhanced production of (1 $\rightarrow$ 3)-${\beta}$-D-glucan by a mutant strain of Agrobacterium species. Biochem Eng J 2003;16:163-8. https://doi.org/10.1016/S1369-703X(03)00032-9
  14. Wu TC, Xu K, Banchereau R, Marches F, Yu CI, Martinek J, Anguiano E, Pedroza-Gonzalez A, Snipes GJ, O'Shaughnessy J, Nishimura S, Liu YJ, Pascual V, Banchereau J, Oh S, Palucka K. Reprogramming tumor-infiltrating dendritic cells for CD103+ CD8+ mucosal T-cell differentiation and breast cancer rejection. Cancer Immunol Res 2014;2:487-500. https://doi.org/10.1158/2326-6066.CIR-13-0217
  15. Rui K, Tian J, Tang X, Ma J, Xu P, Tian X, Wang Y, Xu H, Lu L, Wang S. Curdlan blocks the immune suppression by myeloidderived suppressor cells and reduces tumor burden. Immunol Res 2016;64:931-9. https://doi.org/10.1007/s12026-016-8789-7
  16. Shim JH, Choi WA, Sang BC, Yoon DY. Immune stimulating efficacy of insoluble ${\beta}$-1,3-glucan from Agrobacterium sp. R259 KCTC 10197BP. Yakhak Hoeji 2002;46:459-65.
  17. Lee KH, Park M, Ji KY, Lee HY, Jang JH, Yoon IJ, Oh SS, Kim SM, Jeong YH, Yun CH, Kim MK, Lee IY, Choi HR, Ko KS, Kang HS. Bacterial ${\beta}$-(1,3)-glucan prevents DSS-induced IBD by restoring the reduced population of regulatory T cells. Immunobiology 2014;219:802-12. https://doi.org/10.1016/j.imbio.2014.07.003
  18. Fries R, Konig J, Schafers HJ, Bohm M. Triggering effect of physical and mental stress on spontaneous ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. Clin Cardiol 2002;25:474-8. https://doi.org/10.1002/clc.4960251007
  19. Auinger A, Riede L, Bothe G, Busch R, Gruenwald J. Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body's defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects. Eur J Nutr 2013;52:1913-8. https://doi.org/10.1007/s00394-013-0492-z
  20. Colker CM, Swain M, Lynch L, Gingerich DA. Effects of a milk-based bioactive micronutrient beverage on pain symptoms and activity of adults with osteoarthritis: a double-blind, placebo-controlled clinical evaluation. Nutrition 2002;18:388-92. https://doi.org/10.1016/S0899-9007(01)00800-0
  21. Vetvicka V, Vetvickova J. Glucan supplementation has strong antimelanoma effects: role of NK cells. Anticancer Res 2015;35:5287-92.
  22. Bobovcak M, Kuniakova R, Gabriz J, Majtan J. Effect of Pleuran (${\beta}$-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes. Appl Physiol Nutr Metab 2010;35:755-62. https://doi.org/10.1139/H10-070
  23. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 2004;130:601-30. https://doi.org/10.1037/0033-2909.130.4.601
  24. Priyadarshini S, Aich P. Effects of psychological stress on innate immunity and metabolism in humans: a systematic analysis. PLoS One 2012;7:e43232. https://doi.org/10.1371/journal.pone.0043232
  25. Bush KA, Krukowski K, Eddy JL, Janusek LW, Mathews HL. Glucocorticoid receptor mediated suppression of natural killer cell activity: identification of associated deacetylase and corepressor molecules. Cell Immunol 2012;275:80-9. https://doi.org/10.1016/j.cellimm.2012.02.014
  26. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010;10:170-81. https://doi.org/10.1038/nri2711
  27. Kawashima S, Hirose K, Iwata A, Takahashi K, Ohkubo A, Tamachi T, Ikeda K, Kagami S, Nakajima H. ${\beta}$-glucan curdlan induces IL-10-producing CD4+ T cells and inhibits allergic airway inflammation. J Immunol 2012;189:5713-21. https://doi.org/10.4049/jimmunol.1201521
  28. Elcombe SE, Naqvi S, Van Den Bosch MW, MacKenzie KF, Cianfanelli F, Brown GD, Arthur JS. Dectin-1 regulates IL-10 production via a MSK1/2 and CREB dependent pathway and promotes the induction of regulatory macrophage markers. PLoS One 2013;8:e60086. https://doi.org/10.1371/journal.pone.0060086
  29. Zekovic DB, Kwiatkowski S, Vrvic MM, Jakovljevic D, Moran CA. Natural and modified (1-->3)-${\beta}$-D-glucans in health promotion and disease alleviation. Crit Rev Biotechnol 2005;25:205-30. https://doi.org/10.1080/07388550500376166
  30. Schoenborn JR, Wilson CB. Regulation of interferon-${\gamma}$ during innate and adaptive immune responses. Adv Immunol 2007;96:41-101.
  31. Budak F, Goral G, Oral HB. Saccharomyces cerevisiae beta-glucan induces interferon-gamma production in human T cells via IL-12. Turk J Immunol 2008;13:21-6.
  32. Gattoni A, Parlato A, Vangieri B, Bresciani M, Derna R. Interferongamma: biologic functions and HCV therapy (type I/II) (1 of 2 parts). Clin Ter 2006;157:377-86.
  33. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol 2001;22:633-40. https://doi.org/10.1016/S1471-4906(01)02060-9
  34. Ala Y, Pasha MK, Rao RN, Komaravalli PL, Jahan P. Association of $IFN-{\gamma}$ : IL-10 cytokine ratio with Nonsegmental Vitiligo pathogenesis. Autoimmune Dis 2015;2015:423490.
  35. Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 1991;146:3444-51.
  36. O'Shea D, Cawood TJ, O'Farrelly C, Lynch L. Natural killer cells in obesity: impaired function and increased susceptibility to the effects of cigarette smoke. PLoS One 2010;5:e8660. https://doi.org/10.1371/journal.pone.0008660

Cited by

  1. sp.-derived β-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study vol.11, pp.6, 2017, https://doi.org/10.4162/nrp.2017.11.6.525
  2. Consumption of β-glucans to spice up T cell treatment of tumors: a review vol.18, pp.10, 2018, https://doi.org/10.1080/14712598.2018.1523392
  3. Effects of the Linear Fragments of Beta-(1→3)-Glucans on Cytokine Production in vitro vol.83, pp.8, 2018, https://doi.org/10.1134/S0006297918080114
  4. Effects of Porphyra tenera Supplementation on the Immune System: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial vol.12, pp.6, 2017, https://doi.org/10.3390/nu12061642