Methotrexate (MTX) is used widely for the treatment of a variety of tumors as well as for non-neoplastic conditions. Its association with pneumonitis is well established, but the mechanism of lung injury is unknown. To clarify this issue, we performed bronchoalveolar lavage (BAL) in six patients with MTX pneumonitis and in three control groups. In those with drug-induced pneumonitis, there was a significant increase in the total number of lavage cells recovered as well as in the percentage and absolute number of lymphocytes compared with those in the other groups. Patients receiving the drug without evidence for pulmonary toxicity had lavage findings that were not different from those in the other control groups. The ratio of BAL phenotypic helper/suppressor T-cells was studied in three patients with MTX toxicity and was found to be increased compared with that in normal healthy control subjects. Our findings show that MTX pneumonitis is characterized by a lymphocytic alveolitis with a predominance of phenotypic helper T-cells and a relative deficiency in the percentage of suppressor T-cells. The presence of increased lavage lymphocytes suggests that an immunologically mediated injury rather than a direct toxic effect of this drug may be a significant pathophysiologic mechanism in this disorder.
