Abstract
we investigated the inhibiting effect of the synovial fluid of patients with rheumatoid arthritis (RA) on the induction of indoleamine 2, 3-dioxygenase (IDO) in human macrophage (Mφ) stimulated by interferon-gamma (IFN-γ) . To determine the existence of such an inhibiting facter, we developed an in vitro system for examining the effect of the synovial fluid of RA and osteoarthritis (OA) patients on peripheral blood-derived Mφs. The amounts of tryptophan and kynurenine in the supernatants of cultures were determined by highperformance liquid chromatography. The induction of tryptophan degradation in Mφ was dependent upon the IFN-γ concentration in the culture. Furthermore, IFN-γ regulated mainly the activity of IDO, which is responsible for the conversion of tryptophan to kynurenine. By the addition of RA synovial fluid, the induction of IDO by IFN-γ was significantly decreased in comparison with that of OA.No correlation could be found between the inhibition of IDO activity and the stage and class of RA, or between IDO activity inhibition and inflammatory indeces such as ESR and CRP. These results suggest that IDO in Mφ will be induced by IFN-γ, and that an inhibiting factor for this induction exists in the synovial fluid of RA patients.
