The guinea pig model of diisocyanate sensitization. I. Immunologic studies

Two strains of guinea pigs were parenterally immunized with well-characterized diisocyanate-protein conjugates. Hapten-specific IgE antibodies were detected in the sera of English short-hair strain guinea pigs immunized with either toluene diisocyanate-human serum albumin (TDI-HSA) or hexamethylene diisocyanate-HSA (HDI-HSA) when these sera were analyzed by the 168 hr passive cutaneous anaphylaxis (PCA) technique followed by intravenous challenges with conjugates of respective ligands coupled to an unrelated carrier protein, transferrin. IgG1 antibodies and precipitating antibodies were demonstrated in Hartley strain guinea pigs immunized with TDI/HDI-HSA conjugates. The hapten specificity of these antibodies was proved by PCA inhibition experiments and antibody absorption experiments. In the precipitating antibody system, this was further confirmed by immunoelectrophoretic analysis. Cross-reactivity between HDI and TDI was not observed in the PCA experiments. However, apparent cross-reactivity in the double gel diffusion experiments was due to new antigenic determinants formed by isocyanates after conjugation with proteins. It was therefore apparent that immune responses of guinea pigs immunized with protein conjugates of bifunctional isocyanates were heterogeneous and involved multiple specificities for hapten, carrier protein, and new antigenic determinants. It was postulated that the complex nature of the immune response generated by diisocyanate compounds in the guinea pig may also serve as a more appropriate model of isocyanate-induced human sensitivity reactions, which are known to involve diverse immunologic and nonimmunologic mechanisms.