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

Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation.
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Iverson C, Bacong A, Liu S, Baumgartner S, Lundström T, Oscarsson J, Miner JN,


Iverson C, Bacong A, Liu S, Baumgartner S, Lundström T, Oscarsson J, Miner JN, (click to view)

Iverson C, Bacong A, Liu S, Baumgartner S, Lundström T, Oscarsson J, Miner JN,

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Scientific reports 2018 01 198(1) 1217 doi 10.1038/s41598-018-19252-x
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.

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