title: Different molecular weight hyaluronic acid effects on human macrophage interleukin 1β production.
abstract: This study examined the effect of hyaluronan (HA) molecular weight on immune response. HA with molecular weights ranging from the unitary disaccharide unit (400 Da) up to 1.7 × 10(6) Da and with very low endotoxin contamination level (less than 0.03 EU/mg) was used. Primary human monocyte/macrophage cultures were assayed for IL-1β production under a variety of inflammatory conditions with or without HA. Under the highest inflammatory states, production of interleukin 1β (IL-1β) was suppressed in the presence of high molecular weight hyaluronan (HMW-HA) and in the presence of low molecular weight hyaluronan (LMW-HA) at mg/mL concentrations. There was variability in the sensitivity of the response to HA fragments with MW below 5000 Da at micromolar concentrations. There was variability in IL-1β cytokine productions from donor to donor in unstimulated human cell cultures. This study supplements our previous published study that investigated the immunogenic effect of HA molecular weights using murine cell line RAW264.6, rat splenocytes, and rat adherent differentiated primary macrophages. These data support the hypothesis that if the amount of endotoxin is reduced to an extremely low level, LMW-HA may not directly provoke normal tissue macrophage-mediated inflammatory reactions.
authors.affiliation: Division of Biology, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, FDA, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-002.
authors.forename: Larissa F
authors.initials: LF
authors.lastname: Baeva
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Lyle
authors.forename: Maria
authors.initials: M
authors.lastname: Rios
authors.forename: John J
authors.initials: JJ
authors.lastname: Langone
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Lightfoote
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008422:Materials Testing; D008970:Molecular Weight
chemical_list: D000276:Adjuvants, Immunologic; C508585:IL1B protein, human; D053583:Interleukin-1beta; D006820:Hyaluronic Acid
keywords: biomaterials; hyaluronic acid; inflammation; interleukin 1β; macrophage