IL‐1ß and IL‐8 are scavenged by the hexadecylamide derivative of hyaluronic acid: A new mechanism

Abstract

This study aimed to investigate, using an in vitro model, the mechanisms involved in the effects linked to a novel hexadecylamide derivative of hyaluronic acid (HA), HYADD®4 (HS), on some inflammatory aspects related to the osteoarthritis process. The human leukemic monocytic cell line THP-1 was stimulated with calcium pyrophosphate (CPP) crystals or lipopolysaccaride (LPS) and cultured in the presence of HS or two unmodified HAs (500-730 kDa and >1500 kDa, respectively). The effects of the three HA derivatives were compared by examining the inhibition of IL-1ß and IL-8 release, the phagocytic capacity of THP-1, and HA's physical interference with the cytokines and their biological activity. Adding HS simultaneously with the stimuli led to a marked (nearly 100%) decrease in cytokine release and biological activity with respect to the two unmodified HAs. The effect was not altered when a CD44 function-blocking monoclonal antibody was used. Incubation of the three derivatives with IL-1ß and IL-8 led to a reduced bioavailability of the cytokines in the medium in the presence of HS but not of unmodified HA. This study examines a novel mechanism inhibiting cytokine bioactivity. The HA hexadecylamide derivative was found to suppress, in vitro, the inflammatory response induced by CPP crystals and LPS by reducing the bioavailability of the two cytokines that were analyzed.

Efficacy of a Treatment for Gonarthrosis Based on the Sequential Intra-Articular Injection of Linear and Cross-Linked Hyaluronic Acids

“…The features characterizing the therapeutic course studied herein likely depend on the rational timing of injections with LHA and CLHA, which might exploit and optimize the pharmacokinetic and pharmacodynamics properties of the two forms of HA, in such a way that this regimen results in affordable clinical efficacy and, ultimately, patients' satisfaction. Such an interpretation is in keeping with other and independent evidences indicating that the pharmacodynamic features of HA may profoundly vary as a function of size, structure and chemical modifications (7,9,10,29). These results implicitly suggest that combining different forms of HA such as novel cooperative hybrid complexes or sequential/timed administration of linear and crosslinked preparations as in our case -instead of administering a single, specific form -could recruit multiple and converging mechanisms exalting the pleiotropic nature of native HA.…”

“…Indeed, the HA fragments, depending on their size, display different rheological properties and have been shown to either stimulate or inhibit inflammatory response in targeted cells and in diseased tissues, and to differently modulate the production of specific inflammatory mediators (5,6). In agreement with the notion of the size-and structure-dependent bioactivity of HA, hybrid preparations of low-and high-MW HA (7,8), crosslinked-HA (9) and hexadecylic-derivatized HA (10) show even further variations/ complexity in terms of pharmacodynamics as compared to the native, linear polymers. From the clinical point of view, according to a Cochrane Database Systematic Review analysis based on a significant number of controlled trials, it has been demonstrated that HA injections significantly reduce pain in knee osteoarthritis (11).…”

Specific concentration of hyaluronan amide derivative induces osteogenic mineralization of human mesenchymal stromal cells: Evidence of RUNX2 and COL1A1 genes modulation

“…An hyaluronan amide derivative (HAD) of 500-730 kDa has been produced via amidation of the polymer carboxyl groups by long chain alkylamine (98% remains unmodified HA) to enhance the rheological properties and to increase the residence time in the joint cavity compared with non-amidated unmodified HA (HYAL; Smith, Russell, Schiavinato, & Little, 2013). This HAD biopolymer is an hydrogel and has been shown to exhibit beneficial effects in reducing: (a) cytokines release and biological activity in human monocytic cell line (Oliviero et al, 2015); (b) inflammatory mediators and matrix degradative factors in human OA chondrocytes and synoviocytes (Gabusi et al, 2015;Smith et al, 2013); and (c) lameness and synovial hyperplasia in a sheep model of OA (Smith et al, 2013).…”

“…This HAD biopolymer is an hydrogel and has been shown to exhibit beneficial effects in reducing: (a) cytokines release and biological activity in human monocytic cell line (Oliviero et al, ); (b) inflammatory mediators and matrix degradative factors in human OA chondrocytes and synoviocytes (Gabusi et al, ; Smith et al, ); and (c) lameness and synovial hyperplasia in a sheep model of OA (Smith et al, ).…”

Molecular targets in arthritis and recent trends in nanotherapy

“…It is also well known that HA binds with high affinity to CD44 leading to the inhibition of NF-kB secretion. 20,24 Pathogenesis of RA involves CD4 + T cells, B cells, and monocytes. IL-6 is known to facilitate the differentiation of 25 Cytokines produced by these synovial T cells include TNF-alpha (TNF-α), IFN-γ, and IL-17A.…”