Bronchial Hyperreactivity after Inhalation of Trimellitic Anhydride Dust in Guinea Pigs after Intradermal Sensitization to the Free Hapten

We have developed in the guinea pig, an animal model of bronchial hyperreactivity provoked by inhalation of trimellitic anhydride (TMA) dust, a known cause of occupational asthma in humans, after intradermal sensitization to the free hapten. Male Dunkin-Hartley guinea pigs (n = 6) were injected intradermally with 0.1 ml of 30% TMA in corn oil. Control animals (n = 7) were injected with 0.1 ml corn oil alone. On Days 21 to 28 after sensitization, guinea pigs were challenged (nose only) to 12 mg/m3 of inhalable TMA dust for 30 min. Bronchial reactivity was measured in sensitized animals and in control animals at 8 h after exposure to the dust. We also measured bronchial reactivity in sensitized exposed guinea pigs at 2 h (n = 5) and at 24 h (n = 5). Pulmonary inflation pressure (PIP) was used to assess bronchopulmonary response. Blood samples were taken for assessment of IgG-1 antibodies to TMA conjugated to guinea-pig albumin. The concentration of acetylcholine required to induce a 100% increase in PIP was used to assess bronchial reactivity. The lungs were eviscerated for histologic examination. All guinea pigs injected intradermally with TMA had high titers of specific IgG-1 antibodies to TMA conjugated to guinea-pig albumin. There was a significant increase in bronchial reactivity in sensitized guinea pigs 8 h after exposure to the TMA dust compared with that in the control animals. There was also a significant eosinophilic inflammatory influx in the subepithelium of the sensitized groups.(ABSTRACT TRUNCATED AT 250 WORDS)