Aspirin down‐regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro

• Published in: Clinical and experimental immunology 2005-04, Vol.140 (1), p.41-45
• Main Authors: Schroecksnadel, K., Winkler, C., Wirleitner, B., Schennach, H., Fuchs, D.
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - immunology; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; aspirin; Aspirin - immunology; Aspirin - pharmacology; Basic Immunology; Biological and medical sciences; Cells, Cultured; Concanavalin A - immunology; Down-Regulation - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; indoleamine (2,3)‐dioxygenase (IDO); Kynurenine - analysis; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Medical sciences; neopterin; Neopterin - analysis; Neopterin - biosynthesis; Phytohemagglutinins - immunology; Protein Denaturation - immunology; Salicylic Acid - pharmacology; tryptophan; Tryptophan - analysis; Tryptophan - metabolism
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02746.x

Summary Acetylsalicylic acid (aspirin) is one of the most widely used drugs worldwide, due mainly to its broad therapeutic spectrum with anti‐inflammatory, antipyretic, antithrombotic and analgesic effects. However, the exact mechanisms by which aspirin influences inflammation, pain and immune system activation are only partly understood. Within activation of the cellular immune system, Th1‐type cytokine interferon (IFN)‐γ induces enzyme indoleamine‐2,3‐dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN‐γ induces enzyme GTP‐cyclohydrolase I, which gives rise to neopterin production by activated human macrophages. Similarly, tryptophan degradation and neopterin formation increase during several disease states involving Th1‐type immune activation. Using stimulated human peripheral blood mononuclear cells (PBMC), the effect of aspirin on tryptophan degradation and neopterin production was investigated. Stimulation of PBMC with mitogens concanavalin A, phytohaemagglutinin and pokeweed mitogen induced significant tryptophan catabolism as was reflected by a decline in tryptophan levels and a parallel increase in kynurenine concentrations compared with unstimulated cells. In parallel, neopterin production was enhanced. Treatment of stimulated PBMC with increasing doses of 1–5 mM aspirin significantly decreased stimulation‐induced tryptophan degradation and neopterin production as well. All the effects of aspirin were dose‐dependent. The parallel influence of aspirin on both biochemical pathways implies that there was no direct inhibitory effect of aspirin on IDO; rather, it inhibits production of IFN‐γ in mitogen‐treated PBMC. The influence of aspirin on biochemical pathways induced by IFN‐γ may represent an important part of its broad pharmacological effect.