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 dete rmine its potential to augment pulmonary host defence against Aspergillus., M-CSF (100-600 mug/kg/d) was administered prophylactically to neutropenic rabbits with pulmonary aspergillosis starting three days pre-inoculation an d then throughout neutropenia. Rabbits receiving M-CSF had significantly in creased survival (P = 0.01) and decreased pulmonary injury, as measured by decreased pulmonary infarction (P = 0.004), when compared with untreated co ntrols. Microscopic studies demonstrated greater numbers of activated pulmo nary 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 indic ate that prophylactic administration of M-CSF augments pulmonary host defen ce against A. fumigatus and suggest a potential role for this cytokine as a djunctive therapy in the treatment of pulmonary aspergillosis in the settin g of profound neutropenia. (C) 2001 Academic Press.