Tumor necrosis factor-alpha and lipopolysaccharide enhance interferon-induced antichlamydial indoleamine dioxygenase activity independently

In macrophages, interleukin-1 (IL-1) and lipopolysaccharide (LPS) enhance t he antichlamydial effect of interferon-gamma (IFN-gamma) by increasing indo leamine 2,3-dioxygenase (IDO) activity in a dose-dependent manner. Our obje ctives were to characterize the antichlamydial effect of tumor necrosis fac tor-alpha (TNF-alpha) on IFN-induced IDO activity and to establish the rela tionship between LPS and TNF-alpha in IDO potentiation. TNF-alpha inhibited chlamydial growth in a dose-dependent manner only in IFN-treated macrophag es, Furthermore, excess tryptophan reversed the effect of combined cytokine treatment, indicating that IDO alone was responsible for chlamydial inhibi tion. The promonocyte THP-1 cell line, previously used to model the effect of IL-1 on IDO mRNA expression, was treated with IFN-gamma and increasing c oncentrations of LPS or TNF-alpha, IDO mRNA was quantified by RT-PCR, and I DO activity was measured by HPLC at 24 and 48 h after treatment, respective ly. Both LPS and TNF-alpha enhanced IDO activity and IDO mRNA expression, w ith maximal IDO induction at 100 ng/ml LPS or 5 ng/ml TNF-alpha, Anti-TNF-a lpha failed to neutralize the effects of LPS treatment, and insufficient TN F-alpha or IL-1 was produced by LPS-treated THP-1 cells to account for the enhancing effect of LPS, indicating that the effect of LPS on IDO was indep endent of TNF-alpha and IL-1.