GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERFERON-GAMMAPREVENT DEXAMETHASONE-INDUCED IMMUNOSUPPRESSION OF ANTIFUNGAL MONOCYTE ACTIVITY AGAINST ASPERGILLUS-FUMIGATUS HYPHAE

Treatment with corticosteroids is an important risk factor for develop ment of invasive aspergillosis. We evaluated the effect of dexamethaso ne (DEX) on superoxide anion (O-2(-)) release and damage caused by elu triated human monocytes (EHM) on unopsonized hyphae of Aspergillus fum igatus. 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 concentrati ons of DEX ranging from 5 to 500 nM (1.4-140 ng ml(-1)) for 48 h suppr essed O-2(-) release in response to phorbol myristate acetate in a dos e-dependent fashion. Similarly, DEX significantly suppressed hyphal da mage 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 O-2(-) release and p ercentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effect s of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis.