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Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro.
Clin Exp Immunol. 2005 Apr; 140(1):41-5.CE

Abstract

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)-gamma induces enzyme indoleamine-2,3-dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN-gamma 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-gamma in mitogen-treated PBMC. The influence of aspirin on biochemical pathways induced by IFN-gamma may represent an important part of its broad pharmacological effect.

Authors+Show Affiliations

Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Innsbruck, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15762873

Citation

Schroecksnadel, K, et al. "Aspirin Down-regulates Tryptophan Degradation in Stimulated Human Peripheral Blood Mononuclear Cells in Vitro." Clinical and Experimental Immunology, vol. 140, no. 1, 2005, pp. 41-5.
Schroecksnadel K, Winkler C, Wirleitner B, et al. Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro. Clin Exp Immunol. 2005;140(1):41-5.
Schroecksnadel, K., Winkler, C., Wirleitner, B., Schennach, H., & Fuchs, D. (2005). Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro. Clinical and Experimental Immunology, 140(1), 41-5.
Schroecksnadel K, et al. Aspirin Down-regulates Tryptophan Degradation in Stimulated Human Peripheral Blood Mononuclear Cells in Vitro. Clin Exp Immunol. 2005;140(1):41-5. PubMed PMID: 15762873.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aspirin down-regulates tryptophan degradation in stimulated human peripheral blood mononuclear cells in vitro. AU - Schroecksnadel,K, AU - Winkler,C, AU - Wirleitner,B, AU - Schennach,H, AU - Fuchs,D, PY - 2005/3/15/pubmed PY - 2005/5/17/medline PY - 2005/3/15/entrez SP - 41 EP - 5 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 140 IS - 1 N2 - 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)-gamma induces enzyme indoleamine-2,3-dioxygenase (IDO) which converts tryptophan to kynurenine. In parallel, IFN-gamma 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-gamma in mitogen-treated PBMC. The influence of aspirin on biochemical pathways induced by IFN-gamma may represent an important part of its broad pharmacological effect. SN - 0009-9104 UR - https://www.unboundmedicine.com/medline/citation/15762873/Aspirin_down_regulates_tryptophan_degradation_in_stimulated_human_peripheral_blood_mononuclear_cells_in_vitro_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9104&date=2005&volume=140&issue=1&spage=41 DB - PRIME DP - Unbound Medicine ER -