Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation

Abstract This study assesses the efficacy and exposure–response relationship of omega-3-carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1 macrophages and primary peripheral blood mononuclear cells exposed to multiple inflammatory crystal types were used to determine the...

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Autores principales:	Cory Iverson, Andrew Bacong, Sha Liu, Scott Baumgartner, Torbjörn Lundström, Jan Oscarsson, Jeffrey N. Miner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8b3f9b784464db1890e1f7414d0822b
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spelling	oai:doaj.org-article:f8b3f9b784464db1890e1f7414d0822b2021-12-02T15:08:53ZOmega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation10.1038/s41598-018-19252-x2045-2322https://doaj.org/article/f8b3f9b784464db1890e1f7414d0822b2018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19252-xhttps://doaj.org/toc/2045-2322Abstract This study assesses the efficacy and exposure–response relationship of omega-3-carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1 macrophages and primary peripheral blood mononuclear cells exposed to multiple inflammatory crystal types were used to determine the anti-inflammatory potential of omega-3 (OM-3) fatty acids in vitro. Anti-inflammatory effects of OM-3 CA in vivo were tested in rat monosodium urate (MSU) crystal air pouch and rat knee intra-articular MSU injection models. Acute treatment with the OM-3 fatty acid docosahexaenoic acid suppressed MSU-, cholesterol crystal-, and calcium pyrophosphate crystal-mediated interleukin-1β (IL-1β) production in vitro. In vivo, OM-3 CA dose-dependently reduced crystal-mediated cell migration, exudate volume, and levels of IL-1β and prostaglandin E2. Following intra-articular injection of MSU, treatment with OM-3-CA (1 mL/kg) and indomethacin (1 mg/kg) resulted in similar mean reductions in pain (23% and 41%, respectively) and swelling (58% and 50%, respectively), compared with controls. Additionally, in complex formulations of OM-3 fatty acids, high levels of palmitic acid could reduce the in vivo effect on crystal-mediated IL-1β elevation. OM-3 CA has a broadly efficacious anti-inflammatory effect with a strong exposure–response relationship that could be beneficial in prevention and treatment of crystal arthritis, with potential applications in other IL-1β-mediated diseases.Cory IversonAndrew BacongSha LiuScott BaumgartnerTorbjörn LundströmJan OscarssonJeffrey N. MinerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cory Iverson Andrew Bacong Sha Liu Scott Baumgartner Torbjörn Lundström Jan Oscarsson Jeffrey N. Miner Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
description	Abstract This study assesses the efficacy and exposure–response relationship of omega-3-carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1 macrophages and primary peripheral blood mononuclear cells exposed to multiple inflammatory crystal types were used to determine the anti-inflammatory potential of omega-3 (OM-3) fatty acids in vitro. Anti-inflammatory effects of OM-3 CA in vivo were tested in rat monosodium urate (MSU) crystal air pouch and rat knee intra-articular MSU injection models. Acute treatment with the OM-3 fatty acid docosahexaenoic acid suppressed MSU-, cholesterol crystal-, and calcium pyrophosphate crystal-mediated interleukin-1β (IL-1β) production in vitro. In vivo, OM-3 CA dose-dependently reduced crystal-mediated cell migration, exudate volume, and levels of IL-1β and prostaglandin E2. Following intra-articular injection of MSU, treatment with OM-3-CA (1 mL/kg) and indomethacin (1 mg/kg) resulted in similar mean reductions in pain (23% and 41%, respectively) and swelling (58% and 50%, respectively), compared with controls. Additionally, in complex formulations of OM-3 fatty acids, high levels of palmitic acid could reduce the in vivo effect on crystal-mediated IL-1β elevation. OM-3 CA has a broadly efficacious anti-inflammatory effect with a strong exposure–response relationship that could be beneficial in prevention and treatment of crystal arthritis, with potential applications in other IL-1β-mediated diseases.
format	article
author	Cory Iverson Andrew Bacong Sha Liu Scott Baumgartner Torbjörn Lundström Jan Oscarsson Jeffrey N. Miner
author_facet	Cory Iverson Andrew Bacong Sha Liu Scott Baumgartner Torbjörn Lundström Jan Oscarsson Jeffrey N. Miner
author_sort	Cory Iverson
title	Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
title_short	Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
title_full	Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
title_fullStr	Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
title_full_unstemmed	Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
title_sort	omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f8b3f9b784464db1890e1f7414d0822b
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Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation

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