A MURINE MODEL FOR ASSESSING THE RESPIRATORY HYPERSENSITIVITY POTENTIAL OF CHEMICAL ALLERGENS

Using equimolar quantities of 2 chemical allergens, toluene diisocyana te (TDI), noted for its ability to cause respiratory hypersensitivity, and dinitrochlorobenzene (DNCB), noted for its dermal sensitizing act ivity, the mouse was evaluated as a possible model to indicate respira tory hypersensitivity. A previously published procedure (Garssen et al , (1989) Immunology 68, 51-58) was followed whereby chemicals were app lied epicutaneously to the shaved flank of BALB/c mice. Eight days lat er, animals were challenged by intranasal application of the chemical. The lungs were evaluated at 48 h. Both TDI and DNCB elicited mild mon onuclear inflammatory cuffing around pulmonary vasculature. No reactio n was noted around pulmonary airways. Sera, drawn 48 h following the i ntranasal challenge with chemical allergen, were evaluated for total I gE, hapten-specific IgE and IgG, and for IL-2, IL-4, IL-5, IL-6, and i nterferon gamma. Animals exposed to TDI demonstrated decreased total I gE and the presence of TDI-specific IgG. Cytokine levels were unchange d in both groups. These results indicate that in this mouse model, tot al serum IgE and the production of hapten-specific IgG antibodies dist inguished a respiratory from a contact sensitizing chemical. Further c omparison of the serologic response of mice to these two classes of ch emicals is required to determine if the murine model can be used to pr edict dermal versus respiratory sensitizing activity of chemical aller gens.