Evidence of immunologic control of lung injury induced by trimellitic anhydride.

Trimellitic anhydride (TMA) is a chemical intermediate that has been shown to cause immunologically mediated respiratory syndromes in humans. We developed a rat model in which lung lesions accompanied by TMA-specific antibody resembled effects seen in humans. Two sets of experiments were undertaken to determine if TMA lung injury was primarily controlled by the immune system. Experiment 1: Rats were exposed to 95 micrograms/m3 of TMA 6 h/day, 5 days/wk for 2 wk during which time they received daily injections of either the immunosuppressant cyclophosphamide or saline. The TMA-exposed/saline control rats exhibited the usual TMA-induced lung lesions accompanied by TMA-specific antibody. However, the TMA-exposed/cyclophosphamide rats showed no lesions and no antibody. The spleen cells from all rats were subjected to lymphocyte blastogenesis assays using T- and B-cell mitogens. Results confirmed that cyclophosphamide-treated rats showed very little if any blastogenic response, whereas saline-treated rats gave the normal immune response. Thus, cyclophosphamide eliminated T- and B-cell function, which in turn prevented the occurrence of TMA lesions. Experiment 2: An initial passive transfer experiment showed that serum from TMA-sensitized rats could be adoptively transferred into naive recipient rats, which when given a single TMA inhalation challenge exhibited TMA-induced lesions. Similar attempts to transfer spleen cells or spleen cells plus serum did not predispose recipients for lesions. A second modified passive transfer of sensitized serum using a larger number of recipient rats, followed by a TMA challenge, resulted in lesions in 14 of the 16 rats.(ABSTRACT TRUNCATED AT 250 WORDS)