Immunologic and respiratory responses to airway challenges of dogs with toluene diisocyanate

Abstract

Dogs received biweekly or monthly aerosol immunization with single doses of toluene diisocyanate (TDI) that were cumulative doses analogous to human chronic exposure at 0.02 ppm. The three dogs developed systemic immune responses to TDI-dog serum albumin (DSA). The immune responses included IgG, IgA, and IgM antibody responses and development of lymphocyte reactivity. IgA titers approached IgG titers and both were persistent, whereas IgM titers were low and of short duration. IgE antibody titers demonstrated by endpoint cutaneous titration appeared but fluctuated and became negative in spite of continued aerosol exposure of TDI. Immediate-type airway responses occurred after TDI aerosolization. Some limited responses that showed only abnormalities of selected pulmonary function parameters were clearly not immunologically mediated because they occurred with initial exposure. Other immediate-type airway responses occurred that qualitatively simulated IgE-mediated, antigen-induced airway responses in dogs. There was a statistically significant correlation (p = 0.0268) between these latter airway responses and immediate-type skin reactivity. This study demonstrates that this dog model simulates the complexity of airway responses to TDI in man but may provide a laboratory system for evaluation of immunologic or other proposed mechanisms of TDI asthma.