title: Immunogenicity of hylan g-f 20 in Guinea pigs and mice.
abstract: OBJECTIVE
  To determine the product-specific immunogenicity of a chemically-modified sodium hyaluronate derivative, hylan G-F 20, that is used in the treatment of osteoarthritis of the knee.
  
  
  METHODS
  Guinea pigs were subcutaneously immunized with hylan G-F 20 (Synvisc) once a week for 3 weeks. After resting, these animals received an intradermal challenge with hylan to elicit allergic skin reactions. Animal sera were tested for the presence of hylan-specific antibodies by homologous passive cutaneous anaphylaxis (PCA) assay and of anti-hylan IgG by ELISA. Further, mice were similarly immunized with hylan, and their sera were analyzed by heterologous PCA assay in rats and by ELISA for anti-hylan Ig(G+M) and anti-hylan IgE.
  
  
  RESULTS
  In the guinea pig studies, acute and delayed erythematous skin reactions were elicited in immunized animals after the intradermal challenge with hylan. The sera of hylan-immunized guinea pigs showed positive reaction in the homologous PCA assay and significantly high amount of anti-hylan IgG, whereas the sera did not show any cross-reactivity against sodium hyaluronate. Hylan also exhibited immunogenicity in mice of 3 inbred strains, and C3H/HeN mice showed higher production of anti-hylan antibodies than Balb/c and C57BL/6 mice.
  
  
  CONCLUSIONS
  Hylan G-F 20 exhibited immunogenicity in guinea pigs and mice. Recent reported severe acute inflammatory reactions in human patients after repeated intraarticular injections of hylan G-F 20 might involve product-specific, immune-mediated mechanisms.
authors.affiliation: Central Research Laboratories, Seikagaku Corporation, Tokyo, Japan. sasaki2@seikagaku.co.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Sasaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Takehiko
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toyomi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Miyauchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Iwata
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology; D007106:Immune Sera / Q000008:administration & dosage; D007154:Immune System Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007271:Injections, Intradermal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010323:Passive Cutaneous Anaphylaxis / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013045:Species Specificity
chemical_list: D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C049816:hylan; D006820:Hyaluronic Acid