Differential Effects of Dexamethasone and Itraconazole on <b><i>Aspergillus fumigatus</i></b>-Exacerbated Allergic Airway Inflammation in a Murine Model of Mite-Sensitized Asthma

Abstract

<b><i>Background:</i></b> Fungal exposure is associated with particularly severe asthma. Nevertheless, the effects of anti-fungal treatments on fungus-exacerbated asthma need to be determined. <b><i>Objectives:</i></b> The present study aimed to compare the effects of itraconazole (ITCZ) and dexamethasone (Dex) on <i>Aspergillus fumigatus</i> (<i>Af</i>)-exacerbated preexisting <i>Dermatophagoides farinae</i> (<i>Df</i>) allergen-sensitized allergic airway inflammation. <b><i>Methods:</i></b> Four groups of BALB/c mice were prepared: control, <i>Df</i>-sensitized plus <i>Af</i>-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 <i>Af</i> conidia were determined in <i>Df</i>-sensitized mice. <b><i>Results:</i></b><i>Af</i> infection significantly increased the level of eosinophils and neutrophils in the airway of <i>Df-</i>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 <i>Df</i>-sensitized mice had significantly reduced phagocytotic activity of <i>Af</i> conidia. However, Dex significantly improved phagocytotic activity of AM in <i>Df</i>-sensitized mice. <b><i>Conclusions:</i></b> The present study showed that Dex and ITCZ differently regulated <i>Af</i>-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.