Bacterial Protease Treatment of Natural Rubber Latex Alters Its Primary Immunogenicity in a Mouse Model of Sensitization

The purpose of the present investigation was to determine whether enzyme-treated (ET)-NRL is less immunogenic than untreated NRL in a BALB/c mouse model of primary in vivo sensitization following repeated subcutaneous injections with the aqueous phase of ammoniated NRL or ET-NRL. Mice immunized with NRL produced IgE against NRL and ET-NRL, indicating that protease treatment did not completely destroy IgE antibody epitopes. In contrast, ET-NRL-immunized mice did not produce IgE against either NRL or ET-NRL, suggesting that enzyme treatment reduced the number of antigenic polypeptides associated with NRL below the threshold for sensitization. Thelper-lymphocytes from NRL-immunized mice proliferated and produced IL-4 when stimulated in vitro with polypeptides from NRL, but not ET-NRL. In contrast, Thelper-lymphocytes from ET-NRL-immunized mice were nonresponsive to ET-NRL or NRL. We conclude that lack of IgE production by ET-NRL-immunized mice is likely related to a lack of T-cell help in the form of IL-4, rather than enzyme digestion of IgE antibody epitopes. These data indicate that there is an immunologic rationale for production of enzyme-treated NRL-containing medical devices.