We conducted a placebo-controlled, cross-over trial to examine the effect of Lactobacillus casei Shirota (LcS) on natural killer (NK) cell activity in humans. NK cell activity exhibited a declining trend during the period of placebo ingestion, but NK cell activity increased after intake for 3 weeks of fermented milk containing 4 x 10(10) live LcS. When human peripheral blood mononuclear cells were cultured in the presence of heat-killed LcS, NK cell activity was enhanced. The ability of LcS to enhance NK cell activity and induce interleukin (IL)-12 production was correlated, and the addition of anti-IL-12 monoclonal antibody reduced the enhancement of NK cell activity triggered by LcS. In addition, separation of NK cells from LcS-stimulated monocytes with membrane filter reduced NK cell activity to the intermediate level and almost deprived monocytes of the ability to produce IL-12. These results demonstrate that LcS can enhance NK cell activity in vivo and in vitro in humans, and IL-12 may be responsible for enhancement of NK cell activity triggered by LcS.
