Reversion of the antichlamydial effect of tumor necrosis factor by tryptophan and antibodies to beta interferon

Human recombinant tumor necrosis factor-α (TNF-α) inhibited the growth of Chlamydia trachomatis (L₂/434/Bu) in HEp-2 cells. The effect was synergistic with that of gamma interferon (IFN-γ). TNF-induced resistance to chlamydiae could be blocked with cycloheximide, suggesting that it involves the function of some induced proteins. Tryptophan degradation was enhanced in the TNF-treated cells and was much further increased when the cells were treated with both TNF and IFN-γ at concentrations at which IFN-γ by itself had very little effect. Antibodies to IFN-β blocked the augmentation of tryptophan degradation by TNF and decreased but did not fully eliminate the antichlamydial effect of TNF. Increased concentration of tryptophan in the growth medium (>100 μg/ml) resulted in reversion of the antichlamydial effect of TNF. This study suggests that the inhibition of chlamydial growth by TNF is mediated partly through an autocrine function of IFN-β which, in synergism with TNF, enhances the activity of a tryptophan-degrading enzyme(s) and partly by some other activities of TNF which can be blocked by tryptophan.