Alive and dead Lactobacillus rhamnosus GG decrease tumor necrosis factor-α-induced interleukin-8 production in Caco-2 cells

Certain probiotic bacteria show anti-inflammatory activity after being heat killed, whereas others do not, suggesting that the gastrointestinal environment may alter the activity of probiotic bacteria. Occasionally, probiotics are provided when a patient is also being treated with oral antibiotics; this may have an effect on the probiotic activity. We hypothesized that Lactobacillus rhamnosus GG (LGG) are capable of downregulating tumor necrosis factor-a (TNF alpha)-induced interleukin (IL)-8 production under all 3 of these conditions, and that LGG act through the nuclear factor kappa B (NF kappa B)/inhibitor Of kappa B (I kappa B) pathway. Caco-2 cells were treated with live or heat-killed LGG in doses ranging from 10(4) to 10(10) cfu/L, in the presence or absence of antibiotics and TNF alpha in the media. TNF alpha-induced production of IL-8 by Caco-2 cells was modulated by LGG under all 3 conditions. However, higher doses of live LGG without TNFa in the presence or absence of antibiotics in vitro induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the TNF alpha-induced IL-8 production (P < 0.01), but by itself did not increase IL-8 production at higher doses as markedly as live LGG (P < 0.05). LGG reduced the TNF alpha-induced NF kappa B translocation to the nucleus and lessened the decrease in IKB in the cytoplasm (P < 0.05). LGG reduced TNFa-induced IL-8 production by affecting the NF kappa B/I kappa B pathway in Caco-2 cells. High doses of live LGG markedly increased IL-8 production, but heat-killed LGG caused only a slight increase in IL-8. Thus, heat-killed LGG may effectively ameliorate inflammation with a lower potential than live LGG at high doses to cause inflammation. J. Nutr. 135: 1752-1756, 2005.