Immunogenicity of hylan g-f 20 in Guinea pigs and mice.

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.