title: Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae.
abstract: Treatment with corticosteroids is an important risk factor for development of invasive aspergillosis. We evaluated the effect of dexamethasone (DEX) on superoxide anion (O2-) release and damage caused by elutriated human monocytes (EHM) on unopsonized hyphae of Aspergillus fumigatus. In addition, we studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on these functions of DEX-treated EHM. Treatment of EHM with concentrations of DEX ranging from 5 to 500 nM (1.4-140 ng ml-1) for 48 h suppressed O2- release in response to phorbol myristate acetate in a dose-dependent fashion. Similarly, DEX significantly suppressed hyphal damage caused by EHM as measured by colorimetric MTT assay. Both GM-CSF (5 ng ml-1) and IFN-gamma (1.2 ng ml-1) added at day 0 to the EHM together with DEX (500 nM) significantly enhanced O2- release and percentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effects of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis.
authors.affiliation: Infectious Diseases Section, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: E
authors.initials: E
authors.lastname: Roilides
authors.forename: C
authors.initials: C
authors.lastname: Blake
authors.forename: A
authors.initials: A
authors.lastname: Holmes
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000328:Adult; D001228:Aspergillosis / Q000378:metabolism / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000254:growth & development; D003907:Dexamethasone / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D005938:Glucocorticoids / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D013481:Superoxides; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor