The Additional Effects of Clarithromycin And Pranlukast On The Cytokine Suppression By Corticosteroids Using Murine Allergic Bronchopulmonary Aspergillosis Model

Abstract

Few medicines other than oral corticosteroids and anti-fungal medicines are currently known as reliable treatments for allergic bronchopulmonary aspergillosis (ABPA). The efficacies of macrolide or leukotriene receptor antagonist (LTRA) with or without corticosteroid on ABPA are unknown. Mice were sensitized to Dermatophagoides farinae (Df) allergen intranasally and infected with Aspergillus fumigatus (Af). After Af infection, corticosteroid (Dexamethasone; Dex) was administered for five days in DfAf/Dex group. The effects of macrolide (clarithromycin; CAM) or LTRA (pranlukast; PRN) with or without Dex were also evaluated. Pathologically, the combined treatment with Dex and CAM decreased the airway inflammation. The interleukin (IL)-5, IL-13 and macrophage inflammatory protein (MIP)-2 concentrations in homogenized lungs were significantly elevated in DfAf mice compared to control mice (p < 0.05, each). CAM significantly decreased the elevations of MIP-2 of DfAf mice (p < 0.05). The addition of CAM on Dex suppressed both of the MIP-2 and IL-5 elevation (p < 0.05, each, DfAf/Dex vs DfAf/Dex/CAM group), but the addition of PRN on Dex did not. It was suggested that combination of CAM and corticosteroid enhanced the suppressing effect of both eosinophilic and neutrophilic airway inflammations. This finding will give a new hope for the treatment of severe fungus-related asthma.