Comparison of Interferon‐γ, Granulocyte Colony‐Stimulating Factor, and Granulocyte‐Macrophage Colony‐Stimulating Factor for Priming Leukocyte‐Mediated Hyphal Damage of Opportunistic Fungal Pathogens

Abstract

Proinflammatory cytokines have been proposed as adjunctive therapeutic agents to enhance the host immune response during infections caused by opportunistic fungi. The study compared the differential in vitro priming effects of interferon-gamma (IFN-gamma), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on hyphal damage of opportunistic fungi mediated by isolated neutrophils (polymorphonuclear leukocytes, PMNL) and buffy coat cells (polymorphonuclear leukocytes/peripheral blood mononuclear cells, PMNL/PBMC) from healthy donors. IFN-gamma (1000 U/mL) effectively primed both PMNL and PMNL/PBMC for enhanced hyphal damage of Aspergillus fumigatus, Fusarium solani, and Candida albicans. G-CSF (100 ng/mL) increased hyphal damage mediated by both PMNL and PMNL/PBMC against F. solani, and GM-CSF (100 ng/mL) augmented the antifungal activity of PMNL/PBMC against hyphal forms of both F. solani and C. albicans. IFN-gamma may be superior to G-CSF or GM-CSF for enhancing the microbicidal activity of PMNL and PMNL/PBMC against opportunistic fungi.

Myeloid progenitors protect against invasive aspergillosis andPseudomonas aeruginosa infection following hematopoietic stem cell transplantation

“…The increased survival may be due to the enhancement of neutrophil differentiation, function, and survival following administration of G-CSF. 38,39 These findings suggest that a relatively small increase in either the number of neutrophils or an enhancement of the function of neutrophils in tissue improved destruction of fungal hyphae.…”

Fusarium Infections in Immunocompromised Patients

“…The importance of immunity in the pathogenesis of fusariosis is supported by in vitro and in vivo experimental studies (38,57,94,112), the unique susceptibility of severely immunocompromised patients to disseminated fusariosis (11), and the strong correlation between immune reconstitution and outcome (75).…”

Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3)

“…115 It is well known that PMLs and macrophages constitute an important defense mechanism against the agents of mucormycosis, 116 providing a rationale for the use of granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), and interferon-γ (IFN-γ) as adjunctive treatment beyond the setting of granulocytopenia. GCSF and GM-CSF have been shown to increase phagocytosis, oxidative burst and fungicidal activity of PMLs, [117][118][119][120][121] and IFN-γ to induce a T-helper cell type 1 (Th1) immunological response that favors resistance to invasive fungal infections and enhances PML's antifungal activities. 116,121,122 G-CSF and GMCSF are routinely given to neutropenic patients with invasive fungal diseases including mucormycosis.…”

“…GCSF and GM-CSF have been shown to increase phagocytosis, oxidative burst and fungicidal activity of PMLs, [117][118][119][120][121] and IFN-γ to induce a T-helper cell type 1 (Th1) immunological response that favors resistance to invasive fungal infections and enhances PML's antifungal activities. 116,121,122 G-CSF and GMCSF are routinely given to neutropenic patients with invasive fungal diseases including mucormycosis. The use of γ-IFN in patients with GvHD, a group at high risk for mucormycosis, may augment the aGvH reaction in alloHSCT recipients so as to require augmented immunosuppression for control and thus lead to an even higher risk for invasive fungal infection.…”