A Single-Center, Randomized Double-Blind Placebo-Controlled Study Evaluating the Effects of Poly-Gamma-Glutamate on Human NK Cell Activity after an 8-Week Oral Administration in Healthy Volunteers

Kyung-Soo Kim,Ahrom Kim,Jai-Chul Choi,Sung-Jin Kim,Jang-Hee Hong,Haryoung Poo,Moon-Hee Sung,Tae-Young Lee

doi:10.1155/2013/635960

Abstract

A randomized double-blind placebo-controlled immunity study involving 99 healthy volunteers was performed to investigate the effect of poly-γ-glutamate (γ-PGA) on human natural killer (NK) cell activity in peripheral blood. The volunteers were randomly assigned to one of three groups and orally treated with solutions (25 mL) containing 0 mg (placebo), 250 mg (low dosage), or 500 mg (high dosage) of γ-PGA. Each volunteer took one dose every 12 hours for 8 weeks. Blood samples were drawn before the initial treatment and at the 4th and the 8th weeks of treatment. NK cell activity was assessed by measuring its degranulation, cytokine production, and cytotoxicity against the K562 cell line. Our results revealed that the cytotoxic activities of NK cells from the high-dosage γ-PGA group were significantly higher (P < 0.05 for all comparisons) compared to the low dosage and placebo groups at weeks 4 and 8 after the initial treatment. This increase in the NK cell activity among peripheral blood mononuclear cells (PBMCs) of healthy individuals was also confirmed in vitro (as assessed by the degranulation and cytokine production). These results suggest that the oral administration of γ-PGA induces a cell-mediated immunity by increasing the NK cell activity in humans.

Highlights

Poly-γ-glutamate (γ-PGA), which is naturally secreted from Bacillus, is a safe and edible polymer in which the α-amino and γ-carboxy groups of D- or L-glutamic acid are linked by isopeptide bonds [1]
We investigated the effect of oral administration of highmolecular-weight γ-PGA (MW 2,000 kDa) on the natural killer (NK) cell activity by examining peripheral blood mononuclear cells (PBMCs) from healthy volunteers who were treated in a single-center, randomized double-blind placebo-controlled study
Γ-PGA-treated NK cells produced higher levels of IFN-γ in the presence of K562 cells, compared to untreated samples (Figure 5). These results indicate that the effects observed in γ-PGA-treated donors are consistent with increased levels of NK cell cytotoxic activity and cytokine production

Summary

Introduction

Poly-γ-glutamate (γ-PGA), which is naturally secreted from Bacillus, is a safe and edible polymer in which the α-amino and γ-carboxy groups of D- or L-glutamic acid are linked by isopeptide bonds [1]. Chungkookjang (a traditional Korean food) confers more significant antitumor effects than lower-molecular-mass (10 kDa) γ-PGA by inducing interleukin-12 (IL-12) and interferon-gamma (IFNγ) production and activating natural killer (NK) cells in a mouse model system [2, 3]. These antitumor effects were elicited by the TLR4-dependent stimulation of immune cells (e.g., NK cells), activation of macrophages, and maturation of dendritic cells [3]. As part of their innate effector functions, Evidence-Based Complementary and Alternative Medicine. NK cells destroy targets, including tumor cells, by various mechanisms, and they may be regulated by IL-12 secreted from activated macrophages or dendritic cells [10]

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Conclusion