Liposomal Amphotericin B Fosters the Corticosteroids' Anti-inflammatory Effect on Murine Allergic Bronchopulmonary Aspergillosis Model Airways.

Abstract

Fungus is an antigen for bronchial asthma causing allergic bronchopulmonary mycosis (ABPM). As a therapy other than corticosteroids, itraconazole (ITCZ) is known to suppress the allergic inflammation induced by Aspergillus fumigatus (Af). However, the efficacy of liposomal amphotericin B (LAMB) with/without corticosteroid on ABPM is unknown. Mice sensitized to Dermatophagoides farinae (Df) allergen were intranasally infected with Af (DfAf group). After the infection, corticosteroid (dexamethasone (Dex)) was administered for 5days (DfAf/Dex group). The effects of ITCZ or LAMB with/without Dex were also evaluated. Pathologically, Dex and LAMB combination treatment decreased the allergic inflammation evidently. The bronchoalveolar lavage fluid (BALF) concentrations of IL-5, IL-13, and MIP-2 were significantly elevated in DfAf mice compared with control mice (p < 0.05, each). In DfAf mice, ITCZ and LAMB significantly decreased the elevation of MIP-2 (p < 0.05 vs the DfAf group). The addition of both Dex and LAMB suppressed the MIP-2 elevation in DfAf mice (p < 0.05 vs the Df/Af/Dex/LAMB group), but the addition of Dex and ITCZ did not (DfAf/Dex/ITCZ group). None of Dex, ITCZ, or LAMB decreased pulmonary IL-13 concentration. It was suggested that combination of antifungal drugs and corticosteroid enhanced the suppressing effect of airway inflammations. This finding will give a hope for the treatment of severe fungus-related asthma.