Neutralization of IFNγ exacerbates pneumocystis-driven interstitial pneumonia following bone marrow transplantation in mice

The role of IFNγ in the development of infection-driven interstitial pneumonia in a model of murine graft-versus-host disease was investigated. Mice were given either syngeneic or allogeneic bone marrow transplants (BMT) along with lung Pneumocystis carinii infections and were treated with either control mAb or anti-IFNγ mAb. At day 21 post-BMT, lung weights were elevated nearly 2-fold in all groups. By day 41, mice in all groups had cleared the P. carinii but only the mice given allogeneic BMT and anti-IFNγ had increased lung weights. Increased lung weights in the anti-IFNγ-treated mice corresponded to alveolar infiltration of eosinophils, neutrophils. and multinucleated giant cells and ex-acerbated interstitial pneumonia compared to mice treated with control mAb. Intracellular staining indicated that there were 3 to 10-fold more CD4⁺ cells producing IFNγ than those producing IL-4 in the lung lavages of mice given either syngeneic or allogeneic BMT. Treatment of transplanted mice with anti-IFNγ resulted in a significant decrease in IFNγ-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 IFNγ is critical for controlling the development of P. carinii-driven interstitial pneumonia after either syngeneic or allogeneic BMT in mice.