Alveolar macrophage release of tumor necrosis factor during murine Pneumocystis carinii pneumonia.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine produced principally by mononuclear cells, is released in response to a variety of pulmonary pathogens. We hypothesized that release of TNF in the lung is a normal part of the host response to intratracheal challenge with Pneumocystis carinii. To test this hypothesis, we measured TNF in bronchoalveolar lavage fluid (BALF) in normal and CD4-depleted mice at various intervals in acute and chronically infected animals. To assess the cell of origin and the control of TNF release in the lung, we measured mRNA for TNF by a competitive polymerase chain reaction and assessed the capacity of adherence-enriched cells to produce TNF in vitro in response to lipopolysaccharide. Our data demonstrate that TNF peaks at 3 h in both control and CD4-depleted mice after acute challenge with P. carinii and this increase in TNF precedes the influx of inflammatory cells into the lung. TNF levels in BALF return to undetectable levels by day 3. In chronically infected animals, there is a 5-fold increase in mRNA for TNF in adherent cells which is associated with an increased capacity to release TNF in vitro. These data suggest that TNF is a normal host response to P. carinii infection; however, there is no difference in acute TNF release between control animals that clear their infection and CD4-depleted animals that develop chronic infection. TNF is upregulated in chronically infected animals, but CD4 depletion results in the loss of additional host factors essential for resolution of this infection.
Kolls
J K
JK
Section of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, New Orleans 70112.
Beck
J M
JM
Nelson
S
S
Summer
W R
WR
Shellito
J
J
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002452:Cell Count; D015870:Gene Expression; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011020:Pneumonia, Pneumocystis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha