The guinea pig model of diisocyanate sensitization: II. Physiologic studies

The qualitative and quantitative properties of diisocyanate-specific IgE antisera derived from an IgE-susceptible strain of guinea pigs were investigated by passive sensitization of immunologically virgin recipient animals. These animals received infusions of antisera 48 hr before intravenous challenge with specific ligands conjugated to an unrelated carrier protein, human transferrin. The pulmonary response was sublethal and could be measured by physiologic methods. Various measurements were obtained in anesthetized guinea pigs placed in a whole-body pressure plethysmograph. Tidal volume (V_t), dynamic compliance (C_{L dyn}), and pulmonary conductance (G_L) were calculated from simultaneous recordings of transpulmonary pressure. V_t, and flow. Frequency at 1 and 2 min after intravenous challenge were also measured. Mean respiratory frequency was significantly increased in experimental animals 1 min after challenge with homologous hapten-protein conjugates, while maximum changes of V_t, c_{L dyn}, and G_L occurred 2 min after intravenous challenges. A preponderant number of physiologic abnormalities occurred in animals challenged with homologous hapten-protein conjugates. The mean percent change of V_t and C_{L dyn} from baseline levels was significantly decreased after intravenous challenges with homologous ligands in animals passively sensitized with both hexamethylene diisocyanate—(HDI) and toluene diisocyanate-specific antisera. However, decrease of mean G_L after challenge with homologous hapten-protein conjugates was significant only in animals passively sensitized with HDI-specific antisera. When the number of positive postchallenge pulmonary function responses was compared with the mean geometric titers of IgE antisera, it was observed that moderate or severe physiologic responses were associated with infusions of IgE antisera having titers of 160 or greater. These experiments suggest that antibody concentration may be a critical determinant in distinguishing between clinical, subclinical and nonreactive states induced by diisocyanate sensitization.