Abstract

BackgroundInjection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We have previously developed a protein-free saline-soluble galactomannan derived from guar gum (GM) that displays both analgesia and chondroprotection in experimental osteoarthritis (OA). We now demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection.MethodsMice received 100 μg/25 μL GM or HY or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, interleukin (IL)-1, IL-6, and CXCL-1 (pg/mL) levels were assessed in joint lavage at 6 h. Synovia were excised for histopathology.ResultsNeither GM nor HY after being given into mice knee joints induced pain albeit promoting mild cell influx into joint washings as well as mild synovitis at histology, with no damage to the underlying cartilage. HY but not GM promoted IL-1 release into mice joints. Both compounds induced IL-6 and CXCL-1 release.ConclusionIntra-articular injection of HY or GM promote acute transient synovitis whilst not provoking detectable significant joint damage. Local administration of these polysaccharides induces acute intra-articular release of inflammatory cytokines, which may account for joint flares following viscosupplementation.

Highlights

  • Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants

  • We show that HY as well as a GM solution induce mild acute transient painless synovial cell influx into mice joints that is associated with cytokine release

  • Synovitis The histopathological appearance of the synovia of mice subjected to GM or HY i.art

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Summary

Introduction

Injection of Hylan G-F20 (HY) into joints may provoke local flares, which mechanisms may involve reaction to protein contaminants. We demonstrate that both GM and Hylan G-F20 (HY) promote mild synovitis with cytokine release after intra-articular injection. Viscosupplementation is a commercially available safe alternative to treat osteoarthritis (OA). Such nonsurgical treatment aims to restore viscoelastic properties in diarthrodial joint cavities by injecting viscous hyaluronic acid formulations intra-articularly [1,2,3,4]. It is hard to demonstrate whether viscosupplementation compounds promote synovitis after injection into human healthy joints. In naïve rabbits subjected to an air pouch model, viscosupplements induced a moderate inflammatory reaction and a mild chronic granulomatous reaction following injection into the knee joint [11]

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