Nutr Res Pract.  2017 Feb;11(1):43-50. 10.4162/nrp.2017.11.1.43.

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

Affiliations
  • 1Department of Food and Nutrition, Hanyang University, Wangsimni-ro 222, Seongdong-gu, Seoul 04763, Korea. yongsoon@hanyang.ac.kr
  • 2Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 04763, Korea.
  • 3Devision of Strategic Food Research, Korea Food Research Institute, Seongnam-si, Gyeonggi 13539, Korea.

Abstract

BACKGROUND/OBJECTIVES
The present study investigated the hypothesis that a highly pure linear β-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 4,000-8,000 cells/µL were participated and randomly assigned to take two capsules per day containing either 350 mg β-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)-γ, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-α were measured.
RESULTS
NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the β-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of β-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 β-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration β-1,3-glucan did not significantly modulate the levels of IFN-γ, IL-2, IL-4, IL-6, IL-12, TNF-α and IgG compared with the placebo.
CONCLUSION
The results showed that supplementation with bacterial β-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of β-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.

Keyword

Glucans; natural killer cells; interleukin-10; cytokines; clinical trial

MeSH Terms

Adult*
Agrobacterium*
Capsules
Cytokines
Glucans
Humans
Immunoglobulin G
Interferons
Interleukin-10
Interleukin-12
Interleukin-2
Interleukin-4
Interleukin-6
Interleukins
Killer Cells, Natural*
Leukocyte Count
Reference Values
Smoke
Smoking
Tumor Necrosis Factor-alpha
Capsules
Cytokines
Glucans
Immunoglobulin G
Interferons
Interleukin-10
Interleukin-12
Interleukin-2
Interleukin-4
Interleukin-6
Interleukins
Smoke
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 HPLC chromatogram (A) and structure of β-1,3-glucan (B)

  • Fig. 2 Schematic diagram of study design

  • Fig. 3 Changes in NK cell activity (%) and in the levels of IL-10 (pg/mL) according to stress status. (A) Changes in NK cell activity (%) from baseline to week 8 between the β-glucan and placebo groups. (B) Changes in the levels of IL-10 (pg/mL) from baseline to week 8 between the β-glucan and placebo groups. P-values were determined using an independent t-test.


Cited by  1 articles

Erratum: Agrobacterium sp.-derived β-1,3-glucan enhances natural killer cell activity in healthy adults: a randomized, double-blind, placebo-controlled, parallel-group study
Yeon Joo Lee, Doo-Jin Paik, Dae Young Kwon, Hye Jeong Yang, Yongsoon Park
Nutr Res Pract. 2017;11(6):525-525.    doi: 10.4162/nrp.2017.11.6.525.


Reference

1. Chan GC, Chan WK, Sze DM. The effects of β-glucan on human immune and cancer cells. J Hematol Oncol. 2009; 2:25.
Article
2. Murphy EA, Davis JM, Carmichael MD. Immune modulating effects of β-glucan. Curr Opin Clin Nutr Metab Care. 2010; 13:656–661.
Article
3. Willment JA, Marshall AS, Reid DM, Williams DL, Wong SY, Gordon S, Brown GD. The human β-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. Eur J Immunol. 2005; 35:1539–1547.
Article
4. Mantovani MS, Bellini MF, Angeli JP, Oliveira RJ, Silva AF, Ribeiro LR. β-glucans in promoting health: prevention against mutation and cancer. Mutat Res. 2008; 658:154–161.
Article
5. Yoon TJ, Koppula S, Lee KH. The effects of β-glucans on cancer metastasis. Anticancer Agents Med Chem. 2013; 13:699–708.
6. Heinsbroek SE, Williams DL, Welting O, Meijer SL, Gordon S, de Jonge WJ. Orally delivered β-glucans aggravate dextran sulfate sodium (DSS)-induced intestinal inflammation. Nutr Res. 2015; 35:1106–1112.
Article
7. Kohl A, Gögebakan O, Möhlig M, Osterhoff M, Isken F, Pfeiffer AF, Weickert MO. Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-β-glycan consumption in overweight humans. Nutr Res. 2009; 29:248–254.
Article
8. Nameda S, Harada T, Miura NN, Adachi Y, Yadomae T, Nakajima M, Ohno N. Enhanced cytokine synthesis of leukocytes by a β-glucan preparation, SCG, extracted from a medicinal mushroom, Sparassis crispa. Immunopharmacol Immunotoxicol. 2003; 25:321–335.
Article
9. Bergendiova K, Tibenska E, Majtan J. Pleuran (β-glucan from Pleurotus ostreatus) supplementation, cellular immune response and respiratory tract infections in athletes. Eur J Appl Physiol. 2011; 111:2033–2040.
Article
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; 38:717–719.
11. Nieman DC, Henson DA, McMahon M, Wrieden JL, Davis JM, Murphy EA, Gross SJ, McAnulty LS, Dumke CL. β-glucan, immune function, and upper respiratory tract infections in athletes. Med Sci Sports Exerc. 2008; 40:1463–1471.
Article
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)-β-D-glucan. PLoS One. 2014; 9:e110266.
Article
13. Kim MK, Ryu KE, Choi WA, Rhee YH, Lee IY. Enhanced production of (1 → 3)-β-D-glucan by a mutant strain of Agrobacterium species. Biochem Eng J. 2003; 16:163–168.
Article
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.
Article
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 myeloid-derived suppressor cells and reduces tumor burden. Immunol Res. 2016; 64:931–939.
Article
16. Shim JH, Choi WA, Sang BC, Yoon DY. Immune stimulating efficacy of insoluble β-1,3-glucan from Agrobacterium sp. R259 KCTC 10197BP. Yakhak Hoeji. 2002; 46:459–465.
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 β-(1,3)-glucan prevents DSS-induced IBD by restoring the reduced population of regulatory T cells. Immunobiology. 2014; 219:802–812.
Article
18. Fries R, König J, Schäfers HJ, Böhm M. Triggering effect of physical and mental stress on spontaneous ventricular tachyarrhythmias in patients with implantable cardioverter-defibrillators. Clin Cardiol. 2002; 25:474–478.
Article
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; 52:1913–1918.
Article
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; 18:388–392.
Article
21. Vetvicka V, Vetvickova J. Glucan supplementation has strong anti-melanoma effects: role of NK cells. Anticancer Res. 2015; 35:5287–5292.
22. Bobovčák M, Kuniaková R, Gabriž J, Majtán J. Effect of Pleuran (β-glucan from Pleurotus ostreatus) supplementation on cellular immune response after intensive exercise in elite athletes. Appl Physiol Nutr Metab. 2010; 35:755–762.
Article
23. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004; 130:601–630.
Article
24. Priyadarshini S, Aich P. Effects of psychological stress on innate immunity and metabolism in humans: a systematic analysis. PLoS One. 2012; 7:e43232.
Article
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; 275:80–89.
Article
26. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol. 2010; 10:170–181.
Article
27. Kawashima S, Hirose K, Iwata A, Takahashi K, Ohkubo A, Tamachi T, Ikeda K, Kagami S, Nakajima H. β-glucan curdlan induces IL-10-producing CD4+ T cells and inhibits allergic airway inflammation. J Immunol. 2012; 189:5713–5721.
Article
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.
Article
29. Zeković DB, Kwiatkowski S, Vrvić MM, Jakovljević D, Moran CA. Natural and modified (1-->3)-β-D-glucans in health promotion and disease alleviation. Crit Rev Biotechnol. 2005; 25:205–230.
Article
30. Schoenborn JR, Wilson CB. Regulation of interferon-γ during innate and adaptive immune responses. Adv Immunol. 2007; 96:41–101.
Article
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; 13:21–26.
32. Gattoni A, Parlato A, Vangieri B, Bresciani M, Derna R. Interferon-gamma: biologic functions and HCV therapy (type I/II) (1 of 2 parts). Clin Ter. 2006; 157:377–386.
33. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001; 22:633–640.
Article
34. Ala Y, Pasha MK, Rao RN, Komaravalli PL, Jahan P. Association of IFN-γ : 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; 146:3444–3451.
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.
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