Activation of Macrophages and Cytotoxic Cells during Cytomegalovirus Pneumonia Complicating Lung Transplantations

The functional status of immune cells within human transplanted lungs was analyzed during cytomegalovirus (CMV) pneumonia complicating lung and heart-lung transplantations. The expression of interleukin-1β (IL-1β) and interleukin-6 (IL-6) genes is a marker for the activation of macrophages as is that of serine esterase B (SE-B) gene for cytotoxic cells. The levels of expression of these genes by bronchoalveolar lavage (BAL) cells were determined by in situ hybridization. Eight cases of CMV pneumonia were included in this study. BAL cells from either rejection episodes (eight cases) or control transplanted patients experiencing neither infection nor allograft rejection (eight cases) were analyzed in parallel. In the control patients, virtually no cells expressed the IL-1β, the IL-6, or the SE-B genes. In contrast, these three genes were all expressed in samples from patients with CMV pneumonia. IL-1β gene-expressing cells were abundant in all infected patients (mean ± SEM: 898 ± 449 positive cells per 104 cells, p < 0.001, compared with those in control patients). IL-6 gene-expressing cells were less numerous (92 ± 74 positive cells per 104 cells) and present in five of the eight cases of CMV pneumonia. Activated cytotoxic cells were detected in seven of the eight cases of CMV pneumonia (36.5 ± 19 SE-B gene-expressing cells per 104 cells, p < 0.001). During allograft rejections (eight cases) IL-1β gene-expressing cells were present in all but one patient. However, they were significantly fewer (14.7 ± 6 cells per 104 cells) than during viral pneumonia (p < 0.01). IL-6 gene-expressing cells and SE-B gene-expressing cells were detected in only one of the eight rejection episodes. Therefore, BAL cells express the genes coding for monokines and SE-B during CMV pneumonia in lung-transplanted patients, indicating in situ activation of both macrophages and cytotoxic cells. This activation may play a role in the acute lung dysfunction observed during CMV pneumonia in lung-transplanted patients.