Jk. Kolls et al., ALVEOLAR MACROPHAGE RELEASE OF TUMOR-NECROSIS-FACTOR DURING MURINE PNEUMOCYSTIS-CARINII PNEUMONIA, American journal of respiratory cell and molecular biology, 8(4), 1993, pp. 370-376
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine pr
oduced 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 chall
enge with Pneumocystis carinii. To test this hypothesis, we measured T
NF in bronchoalveolar lavage fluid (BALF) in normal and CD4-depleted m
ice 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 a
nd assessed the capacity of adherence-enriched cells to produce TNF in
vitro in response to lipopolysaccharide. Our data demonstrate that TN
F peaks at 3 h in both control and CD4-depleted mice after acute chall
enge with P carinii and this increase in TNF precedes the influx of in
flammatory cells into the lung. TNF levels in BALF return to undetecta
ble levels by day 3. In chronically infected animals, there is a 5-fol
d 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 cle
ar their infection and CD4-depleted animals that develop chronic infec
tion. TNF is upregulated in chronically infected animals, but CD4 depl
etion results in the loss of additional host factors essential for res
olution of this infection.