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Takeda et al (2006) Interleukin-12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota

Takeda et al (2006) Interleukin-12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota

Citation

Takeda K, Suzuki T, Shimada SI, Shida K, Nanno M and Okumura K (2006) Interleukin-12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota. Clinical &Experimental Immunology 146(1):109-115

Objective

To examine the effect of a daily probiotic containing Lactobacillus casei Shirota (LcS) on natural killer (NK) cell activity in humans and to investigate the mechanisms of action.

[NK cells are types of lymphocytes that are part of the innate immune system, which target virus infected cells and cancer cells].

Methods

In a randomised, placebo-controlled, crossover study, elderly patients (n=10) were supplemented with either a daily probiotic fermented milk drink (4 x 1010 CFU LcS) or a placebo drink with no bacteria, for periods of three weeks, separated after the first intervention by a seven week washout period. Blood samples to measure NK cell activity were taken at baseline, and before and after each intervention period.

The mechanism of activity was investigated by in vitro analysis of peripheral blood mononuclear cells (PBMC) from healthy subjects (n=33). Samples of PBMC were cultured in the presence or absence of LcS for six days, after which cytokines and NK cell activity were measured. Tests were also conducted with the addition of an anti-IL-12 antibody. Additionally, NK cells and monocytes were cultured in chambers separated by a membrane to study the role of cell-to-cell interactions in NK activation. 

Results

At the start of the human study (baseline), NK cell activities in elderly subjects were closely matched. After an intervention period with the probiotic LcS, NK cell activity increased significantly compared with placebo (P <0.05), and was inversely correlated with baseline activity levels.

In vitro analysis of PBMC from healthy subjects showed a similar significant increase in NK cell activity compared to control (P <0.001). There was no increase in the number of NK cells, suggesting that the observed increase in activity occurred at a cellular level. In fact, NK cell activation correlated with the concentration of IL-12 secreted into the supernatant of PBMC in the presence of LcS. Subsequent addition of anti-IL-12 antibody resulted in a significant decrease in the LcS-induced NK cell activity (P <0.05). Cell-to-cell contact between NK cells and monocytes was shown to be important for the LcS-exposed monocytes, to produce IL-12, in order to activate NK cells.

Conclusions

The authors concluded that probiotic intervention with LcS significantly increased NK cell activity in both in vivo and in vitro analysis.

The data indicated that this was mediated at a cellular level, and that the mechanism of activity involved LcS stimulation of monocytes or macrophages to produce IL-12, a cytokine that enhances NK cell activity.

 
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