Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.

Acetylsalicylic acid is a globally used non-steroidal anti-inflammatory drug (NSAID) with diverse pharmacological properties, although its mechanism of immune regulation during inflammation (especially at in vivo relevant doses) remains largely speculative. Given the increase in clinical perspective...

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Autores principales:	Regine Brox, Holger Hackstein
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/af88ee758fb74d4db230e1fdc8b87690
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spelling	oai:doaj.org-article:af88ee758fb74d4db230e1fdc8b876902021-12-02T20:17:39ZPhysiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.1932-620310.1371/journal.pone.0254606https://doaj.org/article/af88ee758fb74d4db230e1fdc8b876902021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254606https://doaj.org/toc/1932-6203Acetylsalicylic acid is a globally used non-steroidal anti-inflammatory drug (NSAID) with diverse pharmacological properties, although its mechanism of immune regulation during inflammation (especially at in vivo relevant doses) remains largely speculative. Given the increase in clinical perspective of Acetylsalicylic acid in various diseases and cancer prevention, this study aimed to investigate the immunomodulatory role of physiological Acetylsalicylic acid concentrations (0.005, 0.02 and 0.2 mg/ml) in a human whole blood of infection-induced inflammation. We describe a simple, highly reliable whole blood assay using an array of toll-like receptor (TLR) ligands 1-9 in order to systematically explore the immunomodulatory activity of Acetylsalicylic acid plasma concentrations in physiologically relevant conditions. Release of inflammatory cytokines and production of prostaglandin E2 (PGE2) were determined directly in plasma supernatant. Experiments demonstrate for the first time that plasma concentrations of Acetylsalicylic acid significantly increased TLR ligand-triggered IL-1β, IL-10, and IL-6 production in a dose-dependent manner. In contrast, indomethacin did not exhibit this capacity, whereas cyclooxygenase (COX)-2 selective NSAID, celecoxib, induced a similar pattern like Acetylsalicylic acid, suggesting a possible relevance of COX-2. Accordingly, we found that exogenous addition of COX downstream product, PGE2, attenuates the TLR ligand-mediated cytokine secretion by augmenting production of anti-inflammatory cytokines and inhibiting release of pro-inflammatory cytokines. Low PGE2 levels were at least involved in the enhanced IL-1β production by Acetylsalicylic acid.Regine BroxHolger HacksteinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0254606 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Regine Brox Holger Hackstein Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
description	Acetylsalicylic acid is a globally used non-steroidal anti-inflammatory drug (NSAID) with diverse pharmacological properties, although its mechanism of immune regulation during inflammation (especially at in vivo relevant doses) remains largely speculative. Given the increase in clinical perspective of Acetylsalicylic acid in various diseases and cancer prevention, this study aimed to investigate the immunomodulatory role of physiological Acetylsalicylic acid concentrations (0.005, 0.02 and 0.2 mg/ml) in a human whole blood of infection-induced inflammation. We describe a simple, highly reliable whole blood assay using an array of toll-like receptor (TLR) ligands 1-9 in order to systematically explore the immunomodulatory activity of Acetylsalicylic acid plasma concentrations in physiologically relevant conditions. Release of inflammatory cytokines and production of prostaglandin E2 (PGE2) were determined directly in plasma supernatant. Experiments demonstrate for the first time that plasma concentrations of Acetylsalicylic acid significantly increased TLR ligand-triggered IL-1β, IL-10, and IL-6 production in a dose-dependent manner. In contrast, indomethacin did not exhibit this capacity, whereas cyclooxygenase (COX)-2 selective NSAID, celecoxib, induced a similar pattern like Acetylsalicylic acid, suggesting a possible relevance of COX-2. Accordingly, we found that exogenous addition of COX downstream product, PGE2, attenuates the TLR ligand-mediated cytokine secretion by augmenting production of anti-inflammatory cytokines and inhibiting release of pro-inflammatory cytokines. Low PGE2 levels were at least involved in the enhanced IL-1β production by Acetylsalicylic acid.
format	article
author	Regine Brox Holger Hackstein
author_facet	Regine Brox Holger Hackstein
author_sort	Regine Brox
title	Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
title_short	Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
title_full	Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
title_fullStr	Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
title_full_unstemmed	Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
title_sort	physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/af88ee758fb74d4db230e1fdc8b87690
work_keys_str_mv	AT reginebrox physiologicallyrelevantaspirinconcentrationstriggerimmunostimulatorycytokineproductionbyhumanleukocytes AT holgerhackstein physiologicallyrelevantaspirinconcentrationstriggerimmunostimulatorycytokineproductionbyhumanleukocytes
_version_	1718374366875484160

Physiologically relevant aspirin concentrations trigger immunostimulatory cytokine production by human leukocytes.

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