STREPTOCOCCAL ERYTHROGENIC TOXINS INDUCE TRYPTOPHAN DEGRADATION IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Background: In various cells including monocytes the cytokine interfer on-gamma as well as lipopolysaccharide induce indoleamine 2,3-dioxygen ase which degrades tryptophan to form L-kynurenine. We addressed the q uestion of whether the exposure of human peripheral mononuclear cells to superantigens derived from streptococci is associated with tryptoph an degradation in vitro. Methods: Peripheral blood mononuclear cells w ere exposed to streptococcal erythrogenic toxins A and B and a strepto coccal-derived mitogen named BX. In addition, the myelomonocytic cell line THP-1 was treated with these toxin preparations. Results: In peri pheral blood mononuclear cells all three toxins induced tryptophan deg radation. In parallel, production of interferon-gamma was found, and t he tryptophan degradation could be blocked by antihuman interferon-gam ma antibodies. Tryptophan degradation was not induced when the human m yelocytoma cell line THP-1 was stimulated with these toxins, but there was a costimulatoty effect to interferon-gamma. Conclusions: In perip heral blood mononuclear cell culture streptococcal erythrogenic toxins are able to stimulate tryptophan degradation in humans via the induct ion of interferon-gamma production. There seems to be no direct effect on myelomonocytic THP-1 cells. Because some of the degradation produc ts of tryptophan, such as quinolinic acid and kynurenic acid, are toxi c, superantigen-driven degradation of tryptophan may play a role for e xample in the development of the toxic-shock-like syndrome associated with severe group A streptococcal infections.