NEUTRALIZATION OF INTERFERON-GAMMA EXACERBATES PNEUMOCYSTIS-DRIVEN INTERSTITIAL PNEUMONITIS AFTER BONE-MARROW TRANSPLANTATION IN MICE

The role of IFN gamma in the development of infection-driven interstit ial pneumonitis in a model of murine graft-versus-host disease was inv estigated. Mice were given either syngeneic or allogeneic bone marrow transplants along with lung Pneumocystis carinii infections and were t reated with either control mAb or anti-IFN gamma mAb. At day 21 after transplant, lung weights were elevated nearly twofold in all groups. B y day 41, mice in all groups had cleared the P. carinii but only the m ice given allogeneic transplants and anti-IFN gamma had increased lung weights, Increased lung weights in the anti-IFN gamma-treated mice co rresponded to alveolar infiltration of eosinophils, neutrophils, and m ultinucleated giant cells and exacerbated interstitial pneumonitis com pared with mice treated with control antibody. Intracellular staining indicated that there were 3- to 10-fold more CD4(+) cells producing IF N gamma than those producing IL-4 in the lung lavages of mice given ei ther syngeneic or allogeneic transplant. Treatment of transplanted mic e with anti-IFN gamma resulted in a significant decrease in IFN gamma- producing CD4(+) and CD8(+) cells in the lung lavages but no change in the number of IL-4-producing CD4(+) cells. These data indicate that I FN gamma is critical for controlling the development of P. carinii-dri ven interstitial pneumonia after either syngeneic or allogeneic bone m arrow transplant in mice.