3-Hydroxy kynurenine treatment controls T. cruzi replication and the inflammatory pathology preventing the clinical symptoms of chronic Chagas disease

PLoS One. 2011;6(10):e26550. doi: 10.1371/journal.pone.0026550. Epub 2011 Oct 19.


Background: 3-Hydroxy Kynurenine (3-HK) administration during the acute phase of Trypanosoma. cruzi infection decreases the parasitemia of lethally infected mice and improves their survival. However, due to the fact that the treatment with 3-HK is unable to eradicate the parasite, together with the known proapoptotic and immunoregulatory properties of 3-HK and their downstream catabolites, it is possible that the 3-HK treatment is effective during the acute phase of the infection by controlling the parasite replication, but at the same time suppressed the protective T cell response before pathogen clearance worsening the chronic phase of the infection. Therefore, in the present study, we investigated the effect of 3-HK treatment on the development of chronic Chagas' disease.

Principal findings: In the present study, we treated mice infected with T. cruzi with 3-HK at day five post infection during 5 consecutive days and investigated the effect of this treatment on the development of chronic Chagas disease. Cardiac functional (electrocardiogram) and histopathological studies were done at 60 dpi. 3-HK treatment markedly reduced the incidence and the severity of the electrocardiogram alterations and the inflammatory infiltrates and fibrosis in heart and skeletal muscle. 3-HK treatment modulated the immune response at the acute phase of the infection impairing the Th1- and Th2-type specific response and inducing TGF-β-secreting cells promoting the emergence of regulatory T cells and long-term specific IFN-γ secreting cells. 3-HK in vitro induced regulatory phenotype in T cells from T. cruzi acutely infected mice.

Conclusions: Our results show that the early 3-HK treatment was effective in reducing the cardiac lesions as well as altering the pattern of the immune response in experimental Chagas' disease. Thus, we propose 3-HK as a novel therapeutic treatment able to control both the parasite replication and the inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chagas Disease / immunology
  • Chagas Disease / parasitology
  • Chagas Disease / prevention & control*
  • Chronic Disease
  • Female
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / parasitology
  • Interferon-gamma / metabolism
  • Kynurenine / analogs & derivatives*
  • Kynurenine / pharmacology
  • Kynurenine / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Species Specificity
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / parasitology
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / immunology
  • Trypanosoma cruzi / pathogenicity
  • Trypanosoma cruzi / physiology*


  • 3-hydroxykynurenine
  • Kynurenine
  • Interferon-gamma