title: In vivo GM-CSF prevents dexamethasone suppression of killing of Aspergillus fumigatus conidia by bronchoalveolar macrophages.
abstract: Dexamethasone (DEX) is a potent immunosuppressive agent used in the treatment of several disorders. However, despite its beneficial effects, DEX puts patients at risk for opportunistic infections, especially pulmonary aspergillosis. Previously we reported that in vitro granulocyte-macrophage colony-stimulating factor (GM-CSF) blocks the immunosuppressive action of DEX on bronchoalveolar macrophages (BAMs). Here we report that BAMs freshly isolated from mice treated intraperitoneally with DEX for 24 h had significantly (P<0.01) reduced killing of conidia, i.e., 15 +/- 5% conidia killed by BAMs from DEX-treated mice versus 35 +/- 3% by BAMs from mice given saline, 38 +/- 5% by BAMs from mice given GM-CSF, and 39 +/- 1% by BAMs from mice given both DEX and GM-CSF. On the other hand, in another compartment GM-CSF could not block the DEX reduction of spleen weight and spleen cellularity. Unlike GM-CSF, granulocyte colony-stimulating factor did not block DEX suppression of BAMs. GM-CSF given 24 h before DEX resulted in blocking of DEX suppression of BAM conidiacidal activity. However, when DEX was given 24 h before GM-CSF, DEX suppression of BAM was not reversed. These data show that GM-CSF in vivo blocks the in vivo immunosuppressive effects of DEX on BAM killing of conidia and suggest a potential use of GM-CSF in patients at risk for aspergillosis due to immunosuppressive DEX treatment.
authors.affiliation: California Institute for Medical Research, Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128-2699, USA. e.brummer@juno.com
authors.forename: E
authors.initials: E
authors.lastname: Brummer
authors.forename: A
authors.initials: A
authors.lastname: Maqbool
authors.forename: D A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor