Recombinant human macrophage colony-stimulating factor augments pulmonary host defences against Aspergillus fumigatus.
The in vivo and ex vivo effects of macrophage colony-stimulating factor (M-CSF) were studied in a profoundly neutropenic rabbit model in order to determine its potential to augment pulmonary host defence against Aspergillus. M-CSF (100-600 microg/kg/d) was administered prophylactically to neutropenic rabbits with pulmonary aspergillosis starting three days pre-inoculation and then throughout neutropenia. Rabbits receiving M-CSF had significantly increased survival (P=0.01) and decreased pulmonary injury, as measured by decreased pulmonary infarction (P=0.004), when compared with untreated controls. Microscopic studies demonstrated greater numbers of activated pulmonary alveolar macrophages (PAMs) in lung tissue of rabbits receiving M-CSF, in comparison to controls (P<0.001). PAMs harvested from rabbits treated with M-CSF had a significantly greater percent phagocytosis of Aspergillus fumigatus conidia than did PAMs from controls (P=0.04). These data indicate that prophylactic administration of M-CSF augments pulmonary host defence against A. fumigatus and suggest a potential role for this cytokine as adjunctive therapy in the treatment of pulmonary aspergillosis in the setting of profound neutropenia.
Gonzalez
C E
CE
Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Lyman
C A
CA
Lee
S
S
Del Guercio
C
C
Roilides
E
E
Bacher
J
J
Gehrt
A
A
Feuerstein
E
E
Tsokos
M
M
Walsh
T J
TJ
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000187:drug effects; D005260:Female; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D011014:Pneumonia / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology; D011655:Pulmonary Embolism / Q000188:drug therapy / Q000473:pathology; D011817:Rabbits; D011994:Recombinant Proteins; D015996:Survival Rate
D000935:Antifungal Agents; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor