Allergy Asthma Immunol Res.  2012 Jul;4(4):214-221. 10.4168/aair.2012.4.4.214.

Therapeutic Effects of Mycobacterial Secretory Proteins Against Established Asthma in BALB/c Mice

• Han ER
• Choi IS
• Choi HG
• Kim HJ

• KMID: 1970710
• DOI: http://doi.org/10.4168/aair.2012.4.4.214

Abstract

PURPOSE
Live/killed mycobacteria and culture supernatants can suppress asthmatic reactions. This study investigated whether mycobacterial secretory proteins have therapeutic effects on asthma.
METHODS
Mycobacterium bovis bacille Calmette-Guerin (BCG; 2x105 CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 microg) were administered intraperitoneally to female BALB/c mice with established airway hyperresponsiveness. One week after treatment, the mice underwent a methacholine challenge test, and then inflammatory cell numbers in bronchoalveolar lavage fluid (BAL) and around bronchi (<500 microm), and cytokine levels in splenocyte supernatants, were assessed.
RESULTS
BCG and all of the tested secretory proteins significantly improved airway sensitivity compared to baseline values (P<0.05). The secretory protein Ag85 complex significantly suppressed airway reactivity also (P<0.05), while 38-kDa protein significantly suppressed reactivity and maximal narrowing (P<0.05). The number of eosinophils in BAL and around bronchi, and the goblet cell proportion, were also significantly reduced in mice in both the BCG and secretory protein groups compared to the asthma control group. IFN-gamma/IL-5 ratios were significantly higher in mice treated with BCG, 4 microg MPB70 or 4 microg 38-kDa protein than in asthma control mice (P<0.05), and were negatively associated with airway hyperresponsiveness, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05). IL-17A was positively correlated with IL-5 (r=0.379, P<0.001), maximal airway narrowing, peribronchial eosinophil numbers and goblet cell proportion (all P<0.05).
CONCLUSIONS
Secretory proteins from BCG and M. tuberculosis and live BCG were effective against established asthma, their effects being accompanied by increased IFN-gamma/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.

Keyword

Ag85 complex; asthma; MPB70; mycobacteria; 38-kDa protein

MeSH Terms

Animals
Asthma
Bronchi
Bronchoalveolar Lavage Fluid
Cell Count
Eosinophils
Female
Goblet Cells
Humans
Indoles
Interleukin-17
Interleukin-5
Methacholine Chloride
Mice
Mycobacterium bovis
Proteins
Tuberculosis
Indoles
Interleukin-17
Interleukin-5
Methacholine Chloride
Proteins

Figure

• 

  Fig. 1 The time course of the experiment. OVA, ovalbumin; ip, intraperitoneal; BCG, bacille Calmette-Guérin; MBPT, methacholine bronchoprovocation test.

• 

  Fig. 2 PC200 was significantly higher in all treatment groups than in the asthma control group. PC200: concentration of methacholine required for a 200% increase in enhanced pause index from baseline. *P<0.05, †P<0.001 vs. the asthma control group.

• 

  Fig. 3 Peribronchial eosinophil numbers and goblet cell proportion in the bronchial epithelium were significantly reduced in all treatment groups compared to the asthma control group. *P<0.05, †P<0.01, ‡P<0.001 vs. the asthma control group.

• 

  Fig. 4 IFN-γ/IL-5 ratios in splenocyte culture supernatants were higher in the BCG, 4 µg MPB70, and 4 µg 38-kDa protein groups than in the asthma control group. *P<0.05, †P<0.001 vs. the asthma control group.

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