We studied the in vitro effects of butyrate on the stimulated release of proinflammatory cytokines and cytokines involved in the Th-1/Th-2 balance using the whole-blood model in nine healthy humans. Cytokines were measured without (control) and after stimulation by bacterial lipopolysaccharides (LPS) and phytohemagglutinin (PHA) alone or with addition of butyrate at six different concentrations (0.0625, 0.125, 0.25, 0.5, 1, and 2 mM). We found that butyrate at the six tested concentrations induced a significant decrease (P < 0.001) in the stimulated release of TNF-alpha, IFN-gamma, and IL-12, whereas IL-6 release was not altered. At concentrations > or = 0.25 mM, butyrate significantly reduced the stimulated release of IL-5, IL-10, and IL-13; the stimulated release of IFN-gamma, IL-12, IL-5, and IL-13 was nearly abolished when compared to the unstimulated control sample. We concluded that butyrate has a wide spectrum of inhibitory activity on cytokine release stimulated by LPS + PHA in a whole-blood model. Confirmation of these results on colonic samples would show that butyrate is a factor by which the luminal contents may modulate the immune system in order to maintain the colonic mucosa in a noninflammatory state.