Research Papers: Immunology:
Itaconic acid indicates cellular but not systemic immune system activation
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Abstract
Johannes Meiser1,2,*, Lisa Kraemer6,*, Christian Jaeger2, Henning Madry3, Andreas Link4, Philipp M. Lepper5, Karsten Hiller2,6,7 and Jochen G. Schneider2,4,8
1Cancer Research UK Beatson Institute, Glasgow, UK
2University of Luxembourg, Luxembourg Centre for Systems Biomedicine, Luxembourg City, Luxembourg
3Saarland University Medical Centre, Centre of Experimental Orthopaedics, Homburg, Germany
4Saarland University Medical Centre, Department of Internal Medicine II, Homburg, Germany
5Saarland University Medical Centre, Department of Internal Medicine V, Homburg, Germany
6Braunschweig Integrated Centre of Systems Biology, Technische Universität Braunschweig, Braunschweig, Germany
7Department of Computational Biology of Infection Research, Helmholtz Centre for Infection Research, Braunschweig, Germany
8Centre Hospitalier Emile Mayrisch, Esch, Luxembourg
*These authors contributed equally to this work
Correspondence to:
Jochen G. Schneider, email: [email protected]
Keywords: itaconic acid; metabolism; sepsis; biomarker; inflammation; Immunology
Received: February 16, 2017 Accepted: July 27, 2018 Published: August 14, 2018
ABSTRACT
Itaconic acid is produced by mammalian leukocytes upon pro-inflammatory activation. It appears to inhibit bacterial growth and to rewire the metabolism of the host cell by inhibiting succinate dehydrogenase. Yet, it is unknown whether itaconic acid acts only intracellularly, locally in a paracrine fashion, or whether it is even secreted from the inflammatory cells at meaningful levels in peripheral blood of patients with severe inflammation or sepsis.
The aim of this study was to determine the release rate of itaconic acid from pro-inflammatory activated macrophages in vitro and to test for the abundance of itaconic acid in bodyfluids of patients suffering from acute inflammation.
We demonstrate that excretion of itaconic acid happens at a low rate and that it cannot be detected in significant amounts in plasma or urine of septic patients or in liquid from bronchial lavage of patients with pulmonary inflammation.
We conclude that itaconic acid may serve as a pro-inflammatory marker in immune cells but that it does not qualify as a biomarker in the tested body fluids.
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