title: Differential effects of dexamethasone and itraconazole on Aspergillus fumigatus-exacerbated allergic airway inflammation in a murine model of mite-sensitized asthma.
abstract: BACKGROUND
  Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined.
  
  
  OBJECTIVE
  The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on Aspergillus fumigatus (Af)-exacerbated preexisting Dermatophagoides farinae (Df) allergen-sensitized allergic airway inflammation.
  
  
  METHODS
  Four groups of BALB/c mice were prepared: control, Df-sensitized plus Af-infected mice (Df-Af), and Df-Af mice treated with Dex (Df-Af-Dex) or with ITCZ (Df-Af-ITCZ). Pulmonary pathology and cytokine profiles in the airway were evaluated. In a different set of experiments, the effects of Dex on alveolar macrophage (AM) phagocytosis of Af conidia were determined in Df-sensitized mice.
  
  
  RESULTS
  Af infection significantly increased the level of eosinophils and neutrophils in the airway of Df-sensitized mice. While Dex significantly decreased eosinophils, ITCZ significantly decreased both eosinophils and neutrophils in Df-Af mice. Dex significantly decreased IL-5, whereas ITCZ significantly reduced MIP-2 in the airway. Compared to controls, AM isolated from Df-sensitized mice had significantly reduced phagocytotic activity of Af conidia. However, Dex significantly improved phagocytotic activity of AM in Df-sensitized mice.
  
  
  CONCLUSIONS
  The present study showed that Dex and ITCZ differently regulated Af-exacerbated allergic airway inflammation; the former inhibits eosinophilic inflammation and the latter inhibits neutrophilic as well as eosinophilic inflammation by regulating different cytokines. Additionally, Dex enhanced the phagocytotic activity of AM in allergic asthma. Thus, a combination of Dex and ITCZ might be effective for the management of fungus-exacerbated asthma.
authors: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan. hmatsuse@nagasaki-u.ac.jp
authors: Hiroto
authors: H
authors: Matsuse
authors: Chizu
authors: C
authors: Fukushima
authors: Susumu
authors: S
authors: Fukahori
authors: Tomoko
authors: T
authors: Tsuchida
authors: Tetsuya
authors: T
authors: Kawano
authors: Tomoya
authors: T
authors: Nishino
authors: Shigeru
authors: S
authors: Kohno
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000935:Antifungal Agents / Q000008:administration & dosage; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000150:complications*; D016207:Cytokines / Q000276:immunology; D040001:Dermatophagoides farinae / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D017964:Itraconazole / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D012137:Respiratory System / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D017964:Itraconazole; D003907:Dexamethasone