Granulocyte-Macrophage Colony Stimulating Factor and <i>Pneumocystis carinii</i> Pneumonia in Mice

Abstract

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 µg/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 < 0.01). 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-α) 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-γ (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-α production.