Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice

• Published in: The Journal of clinical investigation 1997-04, Vol.99 (7), p.1637-1644
• Main Authors: Garvy, B A, Gigliotti, F, Harmsen, A G
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Bone Marrow Transplantation - adverse effects; CD4-Positive T-Lymphocytes - physiology; Female; Graft vs Host Disease - etiology; Interferon-gamma - physiology; Interleukin-4 - biosynthesis; Lung Diseases, Interstitial - etiology; Mice; Mice, Inbred BALB C; Mice, SCID; Pneumonia, Pneumocystis - etiology
• ISSN: 0021-9738
• DOI: 10.1172/JCI119326

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