Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation.
Sci Rep
; 8(1): 1217, 2018 01 19.
Article
em En
| MEDLINE
| ID: mdl-29352206
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-1ß (IL-1ß) production in vitro. In vivo, OM-3 CA dose-dependently reduced crystal-mediated cell migration, exudate volume, and levels of IL-1ß 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-1ß 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-1ß-mediated diseases.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Carboxílicos
/
Artrite Gotosa
/
Ácidos Graxos Ômega-3
/
Anti-Inflamatórios
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article