SPECIFIC IMMUNOLOGICAL AND BRONCHOPULMONARY RESPONSES FOLLOWING INTRADERMAL SENSITIZATION TO FREE TRIMELLITIC ANHYDRIDE IN GUINEA-PIGS

We have developed a guinea pig model of trimellitic anhydride-induced airway hypersensitivity responses. In one group of guinea pigs, injected intradermally with 0.1 ml 30% trimellitic anhydride (TMA), we examined the specificity of the bronchopulmonary response to TMA comparing the effect of intravenous TMA conjugated to guinea pig serum albumin (GPSA) with a control hapten (procion dye) protein conjugate (PD-GPSA). A significant increase in pulmonary inflation pressure (PIP) was provoked in sensitized animals following intravenous injection with TMA-GPSA (20%; 0-400, median, range) as compared to intravenous injection of PD-GPSA. In the second group we compared three different methods of sensitization: single injection of 0.1 ml of 0.3%) TMA; four injections of 0.1 ml of 0.1% TMA; and a single high dose injection of 30% TMA. Following intravenous TMA-GPSA guinea pigs sensitized with a single injection 0.3% TMA had an increase in PIP of 395%; 220-600, while those given four repeat injections of 0.1% TMA had an increase in PIP of 343%; 315-490. These results were significantly higher than the increase in PIP (160%; 0-220) which occurred in guinea pigs sensitized with a single dose of 30% TMA. Four of 11 guinea pigs given low dose injections of TMA had bronchopulmonary responses to inhaled TMA-GPSA. All sensitized guinea pigs had specific IgG1 antibodies demonstrated by enzyme linked immunosorbent assay (ELISA) and confirmed by ELISA inhibition. Four guinea pigs sensitized by low dose injections of TMA had IgE antibodies demonstrated by passive cutaneous anaphylaxis. We conclude that intradermal sensitization to free TMA induces a specific immune and airway hypersensitivity response to TMA-GPSA. Single low dose injection of TMA is the most effective method of sensitization. Intradermal sensitization to free TMA may be a valuable method of sensitization for the developing of an animal model of occupational asthma caused by low molecular weight chemicals.