Immune Response of Dogs and Rabbits to Intrabronchial Trimellitic Anhydride

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Abstract
8 dogs and 7 rabbits were immunized intrabronchially with trimellitic anhydride (TMA) using three different immunizing doses. An immune response occurred in both animal species. Predominantly IgG with lower levels of IgM and IgA antibodies against trimellityl-erythrocytes (TM-E) were detected in both dogs and rabbits. Antibody binding of TM125I dog serum albumin (TM125I-DSA) occurred in most dogs and of TM125I rabbit serum albumin (TM125I-RSA) in 1 out of 7 rabbits. Lymphocyte reactivity was present in all 8 dogs. Death occurred in the 2 dogs immunized with the low dose (0.1 mg/kg) of TMA, in 2 of the 4 dogs immunized with the moderate dose (1.0 mg/kg), and in neither of the 2 dogs immunized repeatedly with the high dose (10.0 mg/kg). No correlation of deaths could be made with serum levels of anti-TM-E antibody or anti-TM125I-DSA antibody binding, or lymphocyte reactivity. The deaths occurred early in the TMA immunizations. All antibody levels in the diseased animals were less than those seen in human workers with TMA-related respiratory disease. Autopsy findings in the 4 dogs showed hemorrhagic pneumonitis possibly analogous to the pulmonary lesions seen in the hemorrhagic pneumonitis of some workers exposed to TMA fumes. TMA as used in these experiments was not toxic to dogs as the high doses of TMA (10.0 mg/kg) did not lead to death which did occur at the lower doses. No deaths occurred in the 7 rabbits immunized with 1.0 mg TMA/kg. The immune responses and pathological findings in dogs encourage further work in the development of animal models of TMA immunologic lung disease.