AIM:To compare the anti-inflammatory properties of butyrate with two other SCFAs, namely acetate and propionate, which have less well-documented effects on inflammation.METHODS: The effect of SCFAs on cytokine release from human neutrophils was studied with ELISA. SCFAdependent modulation of NF-κB reporter activity was assessed in the human colon adenocarcinoma cell line, Colo320DM. Finally, the effect of SCFAs on gene expression and cytokine release, measured with RT-PCR and ELISA, respectively, was studied in mouse colon organ cultures established from colitic mice.RESULTS: Acetate, propionate and butyrate at 30mmol/L decreased LPS-stimulated TNFα release from neutrophils, without affecting IL-8 protein release.All SCFAs dose dependently inhibited NF-κB reporter activity in Colo320DM cells. Propionate dose-dependently suppressed IL-6 mRNA and protein release from colon organ cultures and comparative studies revealed that propionate and butyrate at 30 mmol/L caused a strong inhibition of immune-related gene expression, whereas acetate was less effective. A similar inhibition was achieved with the proteasome inhibitor MG-132, but not the p38 MAPK inhibitor SB203580. All SCFAs decreased IL-6 protein release from organ cultures.CONCLUSION: In the present study propionate and butyrate were equipotent, whereas acetate was less effective, at suppressing NF-κB reporter activity,immune-related gene expression and cytokine release in vitro. Our findings suggest that propionate and acetate, in addition to butyrate, could be useful in the treatment of inflammatory disorders, including IBD.