AB0083 Anti-inflammatory effect of hymovis® on an in vitro model of CPP crystal-induced inflammation. Comparison with other hyaluronic acids used for intra-articular treatment
Authors: F. Oliviero, A. Scanu, P. Frallonardo, R. Ramonda, P. Sfriso, L. Punzi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Intra-articular injections of hyaluronic acid (HA) are widely used in the treatment of inflammatory and degenerative joint diseases. A novel slightly modified hyaluronic acid, HYADD4 (Hymovis®), has recently been tested in an ovine meniscectomy model of osteoarthritis, causing a reduction of vascularity and intimal hyperplasia, and an increase in the synthesis of high molecular weight HA by synovial fibroblasts (1). HYADD4 is a modified hyaluronate where the polysaccharidic backbone is derivatized with hexadecylic (C-16) side chains, through amide bonds, with a 1–3 mol % degree of substitution of repeating units. At a concentration as low as 0.3% (w/v) HYADD4 forms a gel, while unsubstituted hyaluronic acid forms viscous solutions at concentrations that are ten times higher. <h3>Objectives</h3> The purpose of this study is to investigate the effect of HYMOVIS on an in vitro models which reproduces some inflammatory aspects of the osteoarthritis process. <h3>Methods</h3> Synthetic calcium pyrophosphate (CPP) crystals (0.025mg/ml) were used to stimulate a monocytic cell line (THP-1), pre-activated with phorbol myristate acetate 50ng/ml, in presence or absence of Hymovis® (0.5 mg/ml). The production of IL-1β and IL-8 were determined in the supernatants along with the chemoattractant activity on polymorphonuclear cells. The results were compared with those obtained using 2 other types of HA (Hyalubrix® and Hyalgan®). The scavenger effect of Hymovis® on cytokines were investigated through the quantification of the trapping of these proteins to the chemical structure of HYADD4 and the others HA. The stimulation with LPS was used as control. <h3>Results</h3> Hymovis® has shown a strong effect on the inhibition of the production of IL-1β (from 1750±230 pg/ml to 120±52 pg/ml). Although of smaller intensity, this effect was observed also using the other HA (Hymovis&gt;Hyalubrix&gt;Hyalgan). The anti-inflammatory property of Hymovis was also evident on the release of IL-8 (from 2300±315 pg/ml to 150±35 pg/ml) and on the migration of polymorphonuclear cells. The inhibitory effect of IL-8 release was confirmed after stimulation with LPS. All the 3 types of HA have shown to possess a little capacity to trap IL-1β (about 20%) while any scavenger effect was observed towards IL-8. <h3>Conclusions</h3> The hexadecylic derivative of HA Hymovis® has shown a potent anti-inflammatory action on the released of pro-inflammatoy mediators upon stimulation with CPP crystals, frequently associated with more severe and advanced OA. Due to the physical-chemical property of HA preparations, it was likely that its coating on crystals might determine a lower inflammatory activity of crystals themselves. We were able to exclude this hypothesis testing a different stimuli as LPS. The little scavenger effect of all HA towards IL-1β does not account for the observed anti-inflammatory effect as well. It is possible that Hymovis® is able to protect cells from the extracellular compartments where inflammatory stimuli are present. The investigation of IL-1β and IL-8 at the transcriptional level will be evaluated to confirm this hypothesis. <h3>References</h3> MM Smith, MA Cake, P Ghosh, A Schiavinato, R A Read, CB Little. Rheumatology 2008; 47: 1172. <h3>Disclosure of Interest</h3> None Declared