title: 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.
authors.affiliation: Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Oliviero
authors.affiliation: Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Scanu
authors.affiliation: Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ramonda
authors.affiliation: Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Frallonardo
authors.affiliation: Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sfriso
authors.affiliation: Faculty of Medicine, University Medical Center, University of Geneva, Geneva, Switzerland.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dayer
authors.affiliation: Rheumatology Unit, Department of Medicine, DIMED, University of Padova, Padova, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Punzi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008422:Materials Testing; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; C508606:CXCL8 protein, human; D053583:Interleukin-1beta; D016209:Interleukin-8; D006820:Hyaluronic Acid
keywords: hexadecylamide derivative; hyaluronic acid; interleukins; osteoarthritis; pyrophosphate crystals