Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-trypto phan-kynurenine pathway, which converts an essential amino acid, L-tryptoph an, to N-formylkynurenine. It has been speculated that IFN-gamma is a domin ant IDO inducer in vivo. The present study used IFN-gamma or TNF-alpha gene -disrupted mice and IFN-gamma anti body-treated mice to demonstrate that li popolysaccharicle (LPS)-induced systemic IDO is largely dependent on TNF-al pha rather than IFN-gamma. IFN-gamma -independent IDO induction was also de monstrated in vitro with LPS-stimulated monocytic THP-1 cells. These findin gs clearly indicate that there is an IFN-gamma -independent mechanism of ID O induction in addition to the IFN-gamma -dependent mechanism.