Granulocyte-macrophage colony stimulating factor and Pneumocystis carinii pneumonia in mice.
We hypothesized that therapy with granulocyte-macrophage colony stimulating factor (GM-CSF) would decrease intensity of murine Pneumocystis carinii pneumonia by upregulating alveolar macrophage function. Mice were depleted of CD4+ T lymphocytes and then inoculated intratracheally with P. carinii. Four weeks later, they received recombinant murine GM-CSF (rmGM-CSF) 5 micrograms/d subcutaneously for 7 and 14 d. At the end of therapy lung tissue was scored for intensity of P. carinii infection by silver methenamine stain and for inflammation by hematoxylin-eosin stain. We found that rmGM-CSF therapy significant decreased the intensity scores of PCP infection in comparison to control mice (1.88 +/- 0.47 vs 3.06 +/- 0.12, p < 0.001). Inflammation scores were not significantly different in the rmGM-CSF group compared with the control group (1.83 +/- 0.47 vs 2.83 +/- 0.67). Alveolar macrophages from mice treated with rmGM-CSF released significantly more tumor necrosis factor-alpha (TNF-alpha) than cells from control mice after in vitro stimulation with lipopolysaccharide (LPS) alone (2.65 +/- 0.30 vs 1.45 +/- 0.26 ng/ml, p = 0.01) or with LPS plus murine recombinant interferon-gamma (4.16 +/- 0.51 vs 2.25 +/- 0.34 ng/ml, p = 0.01). We conclude that GM-CSF therapy reduces the intensity of PCP and this effect is associated with an enhanced alveolar macrophage TNF-alpha production.
Mandujano
J F
JF
Section of Pulmonary and Critical Care Medicine, Louisiana State University Medical Center, New Orleans 70112.
D'Souza
N B
NB
Nelson
S
S
Summer
W R
WR
Beckerman
R C
RC
Shellito
J E
JE
D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor