Hylan G-F20 and galactomannan joint flares are associated to acute synovitis and release of inflammatory cytokines

Abstract

Background: Injection 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. Methods: Mice 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. Results: Neither 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. Conclusion: Intra-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.

Potent anti-inflammatory activity of the lectin-like domain of TNF in joints

“…Nociceptive behavior was assessed using the electronic pressure meter nociception paw test by an observer blinded to group allocation ( 28 ). Animals were placed in acrylic cages (12 × 10 × 17 cm high) with a wire grid floor, 15 min before the beginning of the tests, in a quiet room.…”

Engineering of Viscosupplement Biomaterials for Treatment of Osteoarthritis: A Comprehensive Review

“…[62] Comparing PRP versus HA viscosupplements in terms of symptoms' relief and time for arthroplasty revealed that the first is associated with better outcomes and might prolong the time for arthroplasty and provide an effective therapeutic option in selected patients with knee OA not responding to conventional A B Reproduced under a Creative Commons Attribution (CC BY 4.0) license. [53] Copyright 2020, The Authors. Published by Springer Nature.…”

“…After 2 months of VS, patients with knee OA previously treated with opioids or IA CS injections exhibited a statistically significant decrease in medication. [ 52 ] Another study on Hylan G‐F20 (HY) demonstrated that both protein‐free saline‐soluble galactomannan derived from guar gum (GM) and Hylan G‐F20 (HY), besides exposing both analgesia and chondroprotection in experimental OA, yield mild synovitis with cytokine release after IA injection [ 53 ] ( Figure ). A study on the long‐term survivorship after 5 years of IA injection of high‐molecular‐weight HA (GF‐20, Synvisc‐One) demonstrated a significantly longer duration of clinical benefit, representing an opportunity to delay the arthroplasty procedure.…”

“…Reproduced under a Creative Commons Attribution (CC BY 4.0) license. [ 53 ] Copyright 2020, The Authors. Published by Springer Nature.…”

“…Figure 3. Main composition of the viscosupplement, A) HA and B) histological images: a) saline-injected joints appearing normal; b) mild synovial hyperplasia (arrowheads) in GM, and c) HY-injected joints at 7 days; d) at 28 days, no long synovial hyperplasia with mild fibrosis in HY (arrow; inset); e) seemingly typical fat subsynovial tissue in a GMinjected joint (dashed arrow) (original magnification: 200Â).Reproduced under a Creative Commons Attribution (CC BY 4.0) license [53]. Copyright 2020, The Authors.…”