Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells

Pro-inflammatory cytokines may directly influence the viability and metabol ic function of colonic epithelial cells (CEC) as an early event in the deve lopment of inflammatory bowel disease. We report here that TNF-alpha+IFN-ga mma induced a synergistic, concentration-dependent decline in butyrate oxid ation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN- gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to p recede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC dam age was independent on NO formation and involved the IFN-gamma signalling p athway as well as induction of apoptosis, If cytokines have similar effects in vivo, these may lead to energy deficiency and thus contribute to CEC da mage and disturbance of the epithelial integrity. (C) 2000 Academic Press.