Immune-mediated inflammation directly impairs pulmonary function, contributing to the pathogenesis of Pneumocystis carinii pneumonia

J Clin Invest. 1999 Nov;104(9):1307-17. doi: 10.1172/JCI6688.


The clinical severity of Pneumocystis carinii pneumonia (PCP) correlates closely with the appearance of pulmonary markers of inflammation. Therefore, a model system was developed whereby physiological studies could be performed on live mice to determine the extent to which pulmonary inflammation contributes to respiratory impairment during PCP. P. carinii-infected severe combined immunodeficient mice displayed little evidence of pulmonary inflammation and exhibited normal oxygenation and dynamic lung compliance. When comparably infected littermates were immunologically reconstituted, however, an intense immune-mediated inflammatory response was observed that resulted in significant decreases in both lung compliance and oxygenation. As the pneumonia resolved pulmonary function returned toward normal. To begin to define the cell populations contributing to inflammation-associated respiratory impairment during PCP, similar studies were performed in CD4(+) T cell-depleted mice. Mice depleted of both CD4(+) and CD8(+) cells developed infection, but they demonstrated neither abnormal lung compliance nor increased respiratory rate and displayed no markers of lung injury. In contrast, mice depleted of only CD4(+) T cells exhibited severe pulmonary inflammation and injury, decreased oxygenation and lung compliance, and increased respirations. Respiratory compromise was associated with the presence of activated CD8(+) cells and neutrophils in broncho-alveolar lavage fluid. These observations provide direct experimental evidence that the host's response to P. carinii directly impairs pulmonary function and contributes to the pathogenesis of PCP. Furthermore, CD8(+) T cells likely contribute to the respiratory compromise observed during PCP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Inflammation*
  • L-Lactate Dehydrogenase / metabolism
  • Lung / immunology
  • Lung / microbiology
  • Lung / physiopathology*
  • Lung Compliance
  • Mice
  • Mice, SCID
  • Oxygen / blood
  • Pneumocystis / metabolism
  • Pneumonia, Pneumocystis / etiology
  • Pneumonia, Pneumocystis / immunology*
  • Respiration
  • Serum Albumin / analysis
  • Time Factors


  • Serum Albumin
  • L-Lactate Dehydrogenase
  • Oxygen