Effects of Inhaled Inactivated Mycobacterium phlei on Airway Inflammation in Mouse Asthmatic Models

Abstract

Corticosteroids are the most efficacious anti-inflammatory drugs for asthma therapy; however, steroids are not always completedly effective for asthma. Studies have shown Mycobacterium bovis Bacille Calmette-Guérin (BCG) and other mycobacterial infections suppress airway hyperresponsiveness and inflammation in asthma. We use a murine model of Ovalbumin (OVA)-induced asthma to study whether nebulized inhalation of inactivated Mycobacterium phlei can alleviate asthmatic airway inflammation through influencing cytokine production and determine whether it can prevent and treat asthma. Fifth male Balb/c mice were randomly divided into four groups: normal control group (A), asthma model group (B0, B3, B4, B5), the treatment group (C0, C3, C4, C5), and prevention group (D). Mice were sensitizated and challenged with Ovalbumin to make a murine asthma model. Group C were given treatment of aerosol Mycobacterium phlei once daily after OVA challenge. Groups C3, C4, and C5 were treated for 3 days, 4 days, and 5 days, respectively. Group D inhaled the solution of inactivated Mycobacterium phlei daily before each time of OVA challenge. All the animals were killed and lung tissue and bronchoalveolar lavage fluid (BALF) were harvested. Pathological HE staining and AB-PAS staining were done to measure lung inflammation and mucus production. Total cell numbers and differential cell count in BALF were performed. Cytokines IL-4, IL-10, and IFN-γ levels in BALF were quantified by ELISA. In groups C4, C5, and D, IL-4 production in BALF was decreased and IL-10 and IFN-γ were increased (p<0.05).The number of total inflammatory cells and the mean percentage of eosinophils and lymphocytes in the BALF of group D, group C4, and group C5 was lower than in the corresponding group B (p<0.05). Histological examination of the lungs showed airway inflammation of group D and group C5 were attenuated. The inhalation of Mycobacterium phlei can reduce airway inflammation in asthmatic mice. This ability was associated with its immunomodulatory effect on regulating IL-4, IL-10, and IFN-γ secretion. Aerosol administration of inactivated Mycobacterium phlei may be accepted as an alternative method with less risk of adverse reactions in treatment of asthma.