In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-01-19)
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 E 2 . 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.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-018-19252-x
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2018
detail.hit.zdb_id:
2615211-3
