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Therapeutic effects of mycobacterial secretory proteins against established asthma in BALB/c mice.

Han ER, Choi IS, Choi HG, Kim HJ - Allergy Asthma Immunol Res (2012)

Bottom Line: 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).Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Allergy, Chonnam National University Medical School, Gwangju, Korea.

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-Guérin (BCG; 2×10(5) CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 µg) 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 µm), 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-γ/IL-5 ratios were significantly higher in mice treated with BCG, 4 µg MPB70 or 4 µg 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-γ/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.

No MeSH data available.


Related in: MedlinePlus

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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Figure 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.

Mentions: In the supernatants of concanavalin A-stimulated splenocytes, the IFN-γ level was significantly lower (499±58 vs. 860±97 pg/mL, P<0.05) and the IL-5 level significantly higher (211±81 vs. 90±10, P<0.001) in the asthma control group than in the normal control group, resulting in a significantly lower IFN-γ/IL-5 in the asthma control group (2.8±0.5 vs. 9.8±1.1, P<0.001) (Fig. 4). The IFN-γ/IL-5 ratio was significantly higher in the groups treated with BCG (5.9±1.1, P<0.05), 4 µg MPB70 (5.6±1.2, P<0.05), and 4 µg 38-kDa protein (5.0±0.8, P<0.05) compared to the asthma control group. The IFN-γ/IL-5 ratio was significantly lower in the group treated with 4 µg Ag85 (3.2±0.4, P<0.05) than in the 4 µg MPB70 group. The IFN-γ/IL-5 ratios for all treatment groups were significantly lower than that for the normal control group. The IL-17A level was significantly higher in the asthma control group than in the normal control group (171.0±22.7 vs. 73.8±7.1 pg/mL, P<0.01). However, IL-17A levels in all treatment groups, while significantly higher than that in the normal control group, were not significantly different than that in the asthma control group.


Therapeutic effects of mycobacterial secretory proteins against established asthma in BALB/c mice.

Han ER, Choi IS, Choi HG, Kim HJ - Allergy Asthma Immunol Res (2012)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3378928&req=5

Figure 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.
Mentions: In the supernatants of concanavalin A-stimulated splenocytes, the IFN-γ level was significantly lower (499±58 vs. 860±97 pg/mL, P<0.05) and the IL-5 level significantly higher (211±81 vs. 90±10, P<0.001) in the asthma control group than in the normal control group, resulting in a significantly lower IFN-γ/IL-5 in the asthma control group (2.8±0.5 vs. 9.8±1.1, P<0.001) (Fig. 4). The IFN-γ/IL-5 ratio was significantly higher in the groups treated with BCG (5.9±1.1, P<0.05), 4 µg MPB70 (5.6±1.2, P<0.05), and 4 µg 38-kDa protein (5.0±0.8, P<0.05) compared to the asthma control group. The IFN-γ/IL-5 ratio was significantly lower in the group treated with 4 µg Ag85 (3.2±0.4, P<0.05) than in the 4 µg MPB70 group. The IFN-γ/IL-5 ratios for all treatment groups were significantly lower than that for the normal control group. The IL-17A level was significantly higher in the asthma control group than in the normal control group (171.0±22.7 vs. 73.8±7.1 pg/mL, P<0.01). However, IL-17A levels in all treatment groups, while significantly higher than that in the normal control group, were not significantly different than that in the asthma control group.

Bottom Line: 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).Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Allergy, Chonnam National University Medical School, Gwangju, Korea.

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-Guérin (BCG; 2×10(5) CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 µg) 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 µm), 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-γ/IL-5 ratios were significantly higher in mice treated with BCG, 4 µg MPB70 or 4 µg 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-γ/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.

No MeSH data available.


Related in: MedlinePlus