Interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis as a direct result of acute lethal graft-versus-host disease duplicate the histopathology of lung allograft rejection.

Pulmonary complications are often lethal components of acute graft-vs.-host disease (GVHD). Although interstitial pneumonitis and lymphocytic bronchitis have been implicated as elements of acute GVHD, previous studies have not determined a correlation between the onset of these histopathologies or their contribution to a pulmonary syndrome that may occur as a direct result of acute GVHD. The present study used the adult, nonirradiated (DA x LEW) F1 hybrid rat in the absence of chemotherapy, immunosuppressive drugs, or overt infection to study these aspects of pulmonary pathology during acute GVHD. F1 animals were intravenously injected with 1 x 10(6) DA parental lymphoid cells/g body weight, which produced 100% morbidity and mortality by day 21. Neither syngeneically injected nor noninjected F1 control animals contained any observable or measurable histopathology. In addition, GVHD and control tissues did not contain bacterial, fungal, or CMV contamination as determined by specific tissue and immunohistochemical staining. GVHD animals were killed on days 3, 7, 10, 14, and 15-21 following injection. Whole-lobe tissue sections (4 mu) were stained with H&E, and histologic alterations within predetermined tissue sites were quantified using light-microscopic image analysis. Alveolar septal widths and perivascular infiltrate volume densities were increased significantly above controls by day 7, and reached 2.4- and 2.6-fold increases, respectively, by day 21. These data corroborated the development of an interstitial pneumonitis and lymphocytic bronchiolitis/bronchitis that duplicated the histopathology of lung allograft rejection. The discovery of pulmonary pathology corresponding to lung allograft rejection during acute GVHD in the adult F1 rat implicates the lung as a potential target organ.