Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae.
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.
Roilides
E
E
Infectious Diseases Section, National Cancer Institute, Bethesda, MD 20892, USA.
Blake
C
C
Holmes
A
A
Pizzo
P A
PA
Walsh
T J
TJ
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*
D005938:Glucocorticoids; D013481:Superoxides; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor