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

Inflammation. 2019 Dec;42(6):2065-2071. doi: 10.1007/s10753-019-01069-z.

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 5 days (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.

Keywords: Dermatophagoides farinae (Df); allergic bronchopulmonary aspergillosis (ABPA); itraconazole (ITCZ); liposomal amphotericin B (LAMB); murine asthma model.

MeSH terms

  • Adrenal Cortex Hormones / pharmacology*
  • Adrenal Cortex Hormones / therapeutic use
  • Amphotericin B / pharmacology*
  • Amphotericin B / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Aspergillosis, Allergic Bronchopulmonary / drug therapy*
  • Aspergillosis, Allergic Bronchopulmonary / microbiology
  • Aspergillosis, Allergic Bronchopulmonary / pathology
  • Aspergillus fumigatus
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Itraconazole / therapeutic use
  • Mice

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antifungal Agents
  • liposomal amphotericin B
  • Itraconazole
  • Dexamethasone
  • Amphotericin B