Anti-inflammatory effects of an injectable copolymer of fatty acids (Ara 3000 beta®) in joint diseases.
BACKGROUND
In inflammatory joint disease, such as osteoarthritis or arthritis, there is an increased level of pro-inflammatory cytokines, such as interleukin-1β. These cytokines stimulate the expression and release of matrix metalloproteases (MMP), leading to the degradation of cartilage extracellular matrix and subsequently mobility difficulty and suffering for patients. The aim of this study was to examine the therapeutic potential of a fatty acid copolymer in in vitro and in vivo models of cartilage inflammation.


METHODS
Inflammation was mimicked in vitro by treatment of human articular chondrocytes with interleukin-1β. Effects of a co-treatment with a copolymer of fatty acids (Ara 3000 beta®) were determined by evaluating MMP production by RT-PCR and ELISA, NO release by Griess assay, and PGE2 expression by ELISA. In addition, in vivo analysis (evolution of weight and edema) were also performed after injection of Freund adjuvant in rats treated or not with the copolymer of fatty acids.


RESULTS
The copolymer of fatty acids clearly reduces inflammation in joint. In vitro, it impairs IL1 stimulated-MMP production and release, as well as the release of NO and PGE2 and the activation of NFκB. Furthermore, in vivo experiments using adjuvant induced-arthritis corroborates the anti-inflammatory effects of the copolymer of fatty acids, with a reduction of edemas, erythemas and ankylosis in arthritic rats.


CONCLUSIONS
The results support the hypothesis that a copolymer of fatty acids, such as Ara 3000 beta®, is a powerful anti-inflammatory compounds, suggesting that it has a potential for preventing cartilage degradation associated with chronic inflammatory joint disease.
Normandie Univ, Caen, France ; UNICAEN, EA4652 MILPAT UFR de médecine, Université de Caen, Caen cedex 5, CS14032 Caen, France.
Catherine
C
Baugé
Normandie Univ, Caen, France ; UNICAEN, EA4652 MILPAT UFR de médecine, Université de Caen, Caen cedex 5, CS14032 Caen, France.
Eva
E
Lhuissier
Normandie Univ, Caen, France ; UNICAEN, EA4652 MILPAT UFR de médecine, Université de Caen, Caen cedex 5, CS14032 Caen, France.
Nicolas
N
Girard
Normandie Univ, Caen, France ; UNICAEN, EA4652 MILPAT UFR de médecine, Université de Caen, Caen cedex 5, CS14032 Caen, France.
Céline
C
Quesnelle
Sexmoor Laboratoires, 13 120 Saint Remy de Provence, France.
Gérard
G
Ewert
Normandie Univ, Caen, France ; UNICAEN, EA4652 MILPAT UFR de médecine, Université de Caen, Caen cedex 5, CS14032 Caen, France.
Karim
K
Boumediene
Arthritis; Cytokines; Drug therapy; Extracellular matrix; Fatty acid; Gene expression; Inflammation; Joints; MMPs; Osteoarthritis