Immunotherapy for Infectious Diseases

310 Casadevall
Table 3
Augmentation of Antifungal Efficacy of Host Effector Cells Against Specific Fungi
by Growth Factors 1
Ref.
Factor Fungus Effect no.
G-CSF Aspergillus fumigatus Prevents PMN and monocyte (80)
suppression by corticosteroids
Aspergillus fumigatus ↑ PMN-induced damage to hyphae (81)
Candida sp. ↑ PMN-induced damage to pseudohyphae (82)
Candida albicans ↑ PMN oxidative burst (83)
Candida albicans ↑ PMN fungicidal activity (84)
Candida albicans Enhances efficacy of azole drugs in mice (85)
Cryptococcus neoformans ↑ PMN fungicidal activity (35)
Cryptococcus neoformans Reversal of HIV-associated PMN (86)
dysfunction
GM-CSF Aspergillus fumigatus Prevents monocyte suppression by (87)
corticosteroids
Candida albicans ↑ Macrophage antifungal activity (88,89)
Cryptococcus neoformans ↑ Monocyte fungistatic activity (90)
Torulopsis glabrata ↑ PMN killing and oxidative burst (91)
M-CSF Candida albicans Enhances fluconazole efficacy (92)
Candida albicans Prolongs survival and reduces organ (93)
fungal burden
Cryptococcus neoformans ↑ Macrophage antifungal activity (94)
Cryptococcus neoformans Synergy with fluconazole in vitro (94,95)
Cryptococcus neoformans ↑ Monocyte fungistatic activity (95)
Abbreviations: CSF, colony-stimulating factor; G, granulocyte; M, macrophage; PMN, polymorphonuclear
leukocyte.
1 This is not a complete list.
fewer bloodstream bacterial infections and no fungal superinfections in patients receiving
G-CSF (38). However, Amphotericin B and G-CSF is not sufficient therapy for
Aspergillus in many patients: Dornbusch et al. (39) reported the cases of five children
treated with combination therapy of whom one was cured, two died, and two required
surgery for removal of pulmonary lesions.
GM-CSF
The effects of GM-CSF are similar to those of G-CSF except that it acts on cells at
an earlier progenitor stage in which cells are capable of differentiating into either granulocyte
or monocyte lineages. Consequently, GM-CSF administration increases not
only PMNs but also eosinophils and monocytes. The increased number of PMNs in
patients given GM-CSF is also a consequence of significantly increased circulating
half-life, which is prolonged from 8 to 48 hours (reviewed in ref. 32). GM-CSF is used
clinically to promote bone marrow recovery after chemotherapy for solid tumors, to
promote engraftment of bone marrow cells, and for treatment of graft failure, aplastic
anemia, and myelodysplastic syndromes. GM-CSF has been shown to enhance phagocytic
cell function against several fungal pathogens (Table 3).