Interleukin-6 (IL-6) may exert anti-inflammatory and protective effects in intestinal mucosa and enterocytes. The influence of probiotics on mucosal and enterocyte IL-6 production is not known. We tested the hypothesis that the probiotic bacteria Lactobacillus paracasei and Lactobacillus plantarum regulate IL-6 production in intestinal epithelial cells. Cultured Caco-2 cells were treated with 1 ng/ml of IL-1 in the absence or presence of different concentrations of Lactobacillus paracasei or Lactobacillus plantarum followed by measurement of IL-6 production. The role of heat shock response was examined by determining the expression of hsp70 and hsp27, by down-regulating their expression with siRNA, or by treating cells with quercetin. Treatment of the Caco-2 cells with IL-1 resulted in increased IL-6 production, confirming previous reports from this laboratory. Probiotics alone did not influence IL-6 production but addition of probitoics to IL-1-treated cells resulted in a substantial augmentation of IL-6 production. Treatment of the Caco-2 cells with live Lactobacillus paracasei increased cellular levels of hsp70 and hsp27 and the potentiating effect on IL-6 production was inhibited by quercetin and by hsp70 or hsp27 siRNA. Results suggest that probiotics may enhance IL-6 production in enterocytes subjected to an inflammatory stimulus and that this effect may, at least in part, be heat shock-dependent.