A MOUSE MODEL FOR STUDY OF LOCALIZED TOLUENE DIISOCYANATE ADDUCTS FOLLOWING INTRABRONCHIAL ADMINISTRATION OF THE CHEMICAL - INFLAMMATION AND ANTIBODY-PRODUCTION

Intranasal and intratracheal administration of chemicals are alternati ve routes to inhalation in some immunologic and toxicologic studies. S election of an appropriate route frequently depends on the physical-ch emical characteristics of the agent, and the desire to avoid aerosol g eneration. We report a simple surgical procedure for site-specific int rabronchial administration of chemicals as a first step in development of a mouse model of chemical asthma. Toluene diisocyanate (TDI), a re cognized cause of occupational asthma, was diluted in corn oil, then a dministered to the left lung lobe through a cannula. Fifteen days late r, mice were challenged by delivery of 1 mu g TDI to the same location . Histopathologic examination 24 h later revealed infiltration of lymp hocytes, neutrophils, and eosinophils around the vasculature and airwa ys. Macrophages were increased in the alveoli. Similar inflammatory re actions were noted in the treated, nonchallenged animals. Immunostaini ng using a rabbit antiserum prepared to a TDI-conjugated protein indic ated TDI adducts localized to the epithelium of the airways and presen t only in the lung lobe that received the chemical. Hapten-specific im munoglobulin G (IgG) antibodies were detected in the circulation, but titers were low and did not correspond with the degree of pulmonary in flammation. These results suggest that this procedure is applicable to development of an animal model of chemically induced asthma in which the role of localized exposure can be elucidated.