INDUCTION OF RESPIRATORY HYPERSENSITIVITY TO DIPHENYLMETHANE-4,4'-DIISOCYANATE (MDI) IN GUINEA-PIGS - INFLUENCE OF ROUTE OF EXPOSURE

The induction of respiratory sensitization in guinea pigs to diphenylm ethane-4,4'-diisocyanate (MDI), a known human respiratory allergen, ha s been investigated and different routes of exposure compared. Guinea pigs were exposed to MDI by i.d. injection, by topical application or by inhalation. Pulmonary hypersensitivity was measured subsequently as a function of changes in respiratory rate following challenge with at mospheres containing MDI. In addition, contact hypersensitivity was me asured by topical challenge and antibody responses evaluated by enzyme -linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA). Attempts to sensitize guinea pigs by inhalation exposure to MDI were unsuccessful. Antibody responses and contact sensitization were both infrequent and low grade, and no animals exhibited pulmonary resp onses following challenge with atmospheric MDI. In contrast, sensitiza tion by either i.d. injection or topical application of MDI induced an tibody responses in the majority of animals. Moreover, a proportion of animals in each case exhibited pulmonary responses following subseque nt inhalation challenge. These data indicate that the route of exposur e influences markedly the effectiveness of sensitization to respirator y allergens such as MDI and that skin contact may be an important caus e of occupational respiratory allergy.