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

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.