Antimalarial drug chloroquine counteracts activation of indoleamine (2,3)-dioxygenase activity in human PBMC

• Published in: FEBS open bio Vol. 2; no. 1; pp. 241 - 245
• Main Authors: Gostner, Johanna M., Schröcksnadel, Sebastian, Becker, Kathrin, Jenny, Marcel, Schennach, Harald, Überall, Florian, Fuchs, Dietmar
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.01.2012; John Wiley & Sons, Inc; Elsevier
• Subjects: Antimalarial agents; Cardiovascular disease; Chloroquine; Cytokines; Dioxygenase; Drug dosages; Gene expression; Indoleamine (2,3)-dioxygenase (IDO); Inflammation; Interferon; Leukocytes (mononuclear); Lupus; Neopterin; PBMC; Peripheral blood mononuclear cells; Rheumatoid arthritis; Therapeutic applications; Tryptophan; United States > US; Austria; Germany; Tryptophan; Indoleamine (2,3)-dioxygenase (IDO); Neopterin; PBMC; Chloroquine
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1016/j.fob.2012.08.004

Antimalarial chloroquine is also used for the treatment of immune-mediated diseases. The interference of chloroquine with interferon-γ-induced tryptophan breakdown and neopterin production has been investigated in human peripheral blood mononuclear cells (PBMC) in vitro. Micromolar concentrations (2–50 μM) of chloroquine dose-dependently suppressed mitogen-induced tryptophan breakdown in PBMC but not in the myelomonocytic THP-1-Blue cell line, after 48 h of treatment. In stimulated PBMC, neopterin production was super-induced by 10 μM chloroquine, while it was significantly suppressed at a concentration of 50 μM. These anti-inflammatory effects may relate to the therapeutic benefit of chloroquine in inflammatory conditions and may widen the spectrum of its clinical applications. ▸ 2–50 μM chloroquine suppresses mitogen-induced tryptophan breakdown in human PBMCs. ▸ The same effect was not seen in the myelomonocytic THP-1-Blue cell line. ▸ The anti-inflammatory property of chloroquine targets T cells more than monocytes. ▸ This anti-inflammatory effect may explain the drug's therapeutic benefit for malaria. ▸ Chloroquine treatment could be of benefit for other chronic inflammatory conditions.