Immunogenicity of Hylan G-F 20 in Guinea Pigs and Mice

Masanori Sasaki, Tatsuya Miyazaki, Takehiko Nakamura, Toyomi Takahashi, Satoshi Miyauchi, Hisashi Iwata

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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. Conclusion. 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.

Original languageEnglish
Pages (from-to)943-950
Number of pages8
JournalJournal of Rheumatology
Issue number5
Publication statusPublished - 2004 May
Externally publishedYes


  • Hylan G-F 20
  • Product-specific immunogenicity
  • Severe acute inflammatory reactions
  • Sodium hyaluronate

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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