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Published in: Lung 5/2017

01-10-2017

The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma

Authors: Chentao Liu, Rong Huang, Rujie Yao, Aimei Yang

Published in: Lung | Issue 5/2017

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Abstract

Introduction

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Recurrent respiratory tract infections in young children, especially viral infections, are the major cause of acute asthmatic exacerbations and contribute to development of asthma. Bacterial extracts have been used to improve the immune defenses of the respiratory tract. However, seldom studies have examined the effect of bacterial lysates on childhood asthma. In this study, we examined whether bacterial lysates (OM-85) will improve symptoms of asthmatic mice via modulation of the immune response.

Methods

Asthmatic mice models were established with OVA challenge and treated with oral administration of Broncho-Vaxom (OM-85). Next, infiltrations of inflammatory cells including eosinophil and neutrophils were examined. Pulmonary tissues in asthmatic mice models were analyzed by hematoxylin and eosin (HE) staining. The levels of Th1/Th2-typed cytokines in bronchoalveolar lavage fluid (BALF) of asthmatic mice models were examined by enzyme-linked immunosorbent assay.

Results

Compared to control group, we found significant reduction of airway wall thickness, luminal stenosis, and mucus plug formation in asthmatic mice models after oral administration of OM-85. The infiltrations of eosinophil were also significantly decreased in BALF in asthmatic mice models. Oral administration of OM-85 was shown to suppress Th2-type cytokine levels.

Conclusion

Our findings provide evidence that oral administration of OM-85 is capable of attenuating airway inflammation in asthmatic mice models. Oral administration of OM-85 may have a positive impact in terms of asthma severity.
Literature
1.
go back to reference Kusel MM, de Klerk NH, Kebadze T et al (2007) Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol 119(5):1105–1110CrossRefPubMed Kusel MM, de Klerk NH, Kebadze T et al (2007) Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma. J Allergy Clin Immunol 119(5):1105–1110CrossRefPubMed
2.
go back to reference Sly PD, Kusel M, Holt PG (2010) Do early-life viral infections cause asthma? J Allergy Clin Immunol 125(6):1202–1205CrossRefPubMed Sly PD, Kusel M, Holt PG (2010) Do early-life viral infections cause asthma? J Allergy Clin Immunol 125(6):1202–1205CrossRefPubMed
3.
go back to reference Jackson DJ, Gangnon RE, Evans MD et al (2008) Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 178(7):667–672CrossRefPubMedPubMedCentral Jackson DJ, Gangnon RE, Evans MD et al (2008) Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med 178(7):667–672CrossRefPubMedPubMedCentral
4.
go back to reference Murray CS, Poletti G, Kebadze T et al (2006) Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61(5):376–382CrossRefPubMed Murray CS, Poletti G, Kebadze T et al (2006) Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Thorax 61(5):376–382CrossRefPubMed
5.
go back to reference Heymann PW, Carper HT, Murphy DD et al (2004) Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol 114(2):239–247CrossRefPubMed Heymann PW, Carper HT, Murphy DD et al (2004) Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol 114(2):239–247CrossRefPubMed
6.
go back to reference Inoue Y, Shimojo N (2013) Epidemiology of virus-induced wheezing/asthma in children. Front Microbiol 16(4):391 Inoue Y, Shimojo N (2013) Epidemiology of virus-induced wheezing/asthma in children. Front Microbiol 16(4):391
7.
go back to reference Jackson DJ, Lemanske RF Jr (2010) The role of respiratory virus infections in childhood asthma inception. Immunol Allergy Clin N Am 30(4):513–522CrossRef Jackson DJ, Lemanske RF Jr (2010) The role of respiratory virus infections in childhood asthma inception. Immunol Allergy Clin N Am 30(4):513–522CrossRef
8.
go back to reference Linder JE, Kraft DC, Mohamed Y et al (2013) Human rhinovirus C: age, season, and lower respiratory illness over the past 3 decades. J Allergy Clin Immunol 131(1):69–77CrossRefPubMed Linder JE, Kraft DC, Mohamed Y et al (2013) Human rhinovirus C: age, season, and lower respiratory illness over the past 3 decades. J Allergy Clin Immunol 131(1):69–77CrossRefPubMed
10.
go back to reference Ahanchian H, Jones CM, Chen YS et al (2012) Respiratory viral infections in children with asthma: do they matter and can we prevent them? BMC Pediatr 13(12):147 Ahanchian H, Jones CM, Chen YS et al (2012) Respiratory viral infections in children with asthma: do they matter and can we prevent them? BMC Pediatr 13(12):147
11.
go back to reference Wu P, Hartert TV (2011) Evidence for a causal relationship between respiratory syncytial virus infection and asthma. Expert Rev Anti Infect Ther 9(9):731–745CrossRefPubMedPubMedCentral Wu P, Hartert TV (2011) Evidence for a causal relationship between respiratory syncytial virus infection and asthma. Expert Rev Anti Infect Ther 9(9):731–745CrossRefPubMedPubMedCentral
13.
go back to reference De Benedetto F, Sevieri G (2013) Prevention of respiratory tract infections with bacterial lysate OM-85 bronchomunal in children and adults: a state of the art. Multidiscip Respir Med 8(1):33CrossRefPubMedPubMedCentral De Benedetto F, Sevieri G (2013) Prevention of respiratory tract infections with bacterial lysate OM-85 bronchomunal in children and adults: a state of the art. Multidiscip Respir Med 8(1):33CrossRefPubMedPubMedCentral
14.
go back to reference Ahrens B, Quarcoo D, Buhner S et al (2011) Oral administration of bacterial lysates attenuates experimental food allergy. Int Arch Allergy Immunol 156(2):196–204CrossRefPubMed Ahrens B, Quarcoo D, Buhner S et al (2011) Oral administration of bacterial lysates attenuates experimental food allergy. Int Arch Allergy Immunol 156(2):196–204CrossRefPubMed
15.
go back to reference Lau S (2013) Oral application of bacterial lysate in infancy diminishes the prevalence of atopic dermatitis in children at risk for atopy. Benef Microbes 25:1–3 Lau S (2013) Oral application of bacterial lysate in infancy diminishes the prevalence of atopic dermatitis in children at risk for atopy. Benef Microbes 25:1–3
16.
go back to reference Lu Y, Li Y, Xu L et al (2015) Bacterial lysate increases the percentage of natural killer T cells in peripheral blood and alleviates asthma in children. Pharmacology 95(3–4):139–144CrossRefPubMed Lu Y, Li Y, Xu L et al (2015) Bacterial lysate increases the percentage of natural killer T cells in peripheral blood and alleviates asthma in children. Pharmacology 95(3–4):139–144CrossRefPubMed
17.
go back to reference Vissers JL, van Esch BC, Hofman GA et al (2004) Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J Allergy Clin Immunol 113(6):1204–1210CrossRefPubMed Vissers JL, van Esch BC, Hofman GA et al (2004) Allergen immunotherapy induces a suppressive memory response mediated by IL-10 in a mouse asthma model. J Allergy Clin Immunol 113(6):1204–1210CrossRefPubMed
18.
go back to reference Ford JG, Rennick D, Donaldson DD et al (2001) Il-13 and IFN-gamma: interactions in lung inflammation. J Immunol 167(3):1769–1777CrossRefPubMed Ford JG, Rennick D, Donaldson DD et al (2001) Il-13 and IFN-gamma: interactions in lung inflammation. J Immunol 167(3):1769–1777CrossRefPubMed
19.
go back to reference Sagar S, Verheijden KA, Georgiou NA et al (2013) Differential regulation of inflammation and immunity in mild and severe experimental asthma. Mediat Inflamm 2013:808470CrossRef Sagar S, Verheijden KA, Georgiou NA et al (2013) Differential regulation of inflammation and immunity in mild and severe experimental asthma. Mediat Inflamm 2013:808470CrossRef
20.
21.
go back to reference Bogaert P, Tournoy KG, Naessens T et al (2009) Where asthma and hypersensitivity pneumonitis meet and differ: noneosinophilic severe asthma. Am J Pathol 174(1):3–13CrossRefPubMedPubMedCentral Bogaert P, Tournoy KG, Naessens T et al (2009) Where asthma and hypersensitivity pneumonitis meet and differ: noneosinophilic severe asthma. Am J Pathol 174(1):3–13CrossRefPubMedPubMedCentral
22.
go back to reference Fahy JV (2009) Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc 6(3):256–259CrossRefPubMed Fahy JV (2009) Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc 6(3):256–259CrossRefPubMed
23.
go back to reference Antoniu SA (2010) MEDI-528, an anti-IL-9 humanized antibody for the treatment of asthma. Curr Opin Mol Ther 12:233–239PubMed Antoniu SA (2010) MEDI-528, an anti-IL-9 humanized antibody for the treatment of asthma. Curr Opin Mol Ther 12:233–239PubMed
24.
go back to reference Gauvreau GM, Boulet LP, Cockcroft DW et al (2011) Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med 183:1007–1014CrossRefPubMed Gauvreau GM, Boulet LP, Cockcroft DW et al (2011) Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med 183:1007–1014CrossRefPubMed
25.
26.
go back to reference Okayama Y (2013) Cellular and humoral immunity of virus-induced asthma. Front Microbiol 27(4):252 Okayama Y (2013) Cellular and humoral immunity of virus-induced asthma. Front Microbiol 27(4):252
27.
go back to reference Jackson DJ, Lemanske RF Jr (2010) The role of respiratory virus infections in childhood asthma inception. Immunol Allergy Clin N Am 30(4):513–522CrossRef Jackson DJ, Lemanske RF Jr (2010) The role of respiratory virus infections in childhood asthma inception. Immunol Allergy Clin N Am 30(4):513–522CrossRef
29.
go back to reference Podleski WK (1985) Immunomodulation of allergic autocytotoxicity in bronchial asthma by a bacterial lysate–Broncho-Vaxom. Int J Immunopharmacol 7(5):713–718CrossRefPubMed Podleski WK (1985) Immunomodulation of allergic autocytotoxicity in bronchial asthma by a bacterial lysate–Broncho-Vaxom. Int J Immunopharmacol 7(5):713–718CrossRefPubMed
30.
go back to reference Weinberger M (2010) Can we prevent exacerbations of asthma caused by common cold viruses? J Allergy Clin Immunol. 126(4):770–771CrossRefPubMed Weinberger M (2010) Can we prevent exacerbations of asthma caused by common cold viruses? J Allergy Clin Immunol. 126(4):770–771CrossRefPubMed
31.
go back to reference Schaad UB (2010) OM-85 BV, an immunostimulant in pediatric recurrent respiratory tract infections: a systematic review. World J Pediatr 6(1):5–12CrossRefPubMed Schaad UB (2010) OM-85 BV, an immunostimulant in pediatric recurrent respiratory tract infections: a systematic review. World J Pediatr 6(1):5–12CrossRefPubMed
32.
go back to reference Razi CH, Harmancı K, Abacı A et al (2010) The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol 126(4):763–769CrossRefPubMed Razi CH, Harmancı K, Abacı A et al (2010) The immunostimulant OM-85 BV prevents wheezing attacks in preschool children. J Allergy Clin Immunol 126(4):763–769CrossRefPubMed
33.
go back to reference Rozy A, Chorostowska-Wynimko J (2008) Bacterial immunostimulants—mechanism of action and clinical application in respiratory diseases. Pneumonol Alergol Pol 76(5):353–359PubMed Rozy A, Chorostowska-Wynimko J (2008) Bacterial immunostimulants—mechanism of action and clinical application in respiratory diseases. Pneumonol Alergol Pol 76(5):353–359PubMed
34.
go back to reference Strickland DH, Judd S, Thomas JA et al (2011) Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control. Mucosal Immunol 4:43–52CrossRefPubMed Strickland DH, Judd S, Thomas JA et al (2011) Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control. Mucosal Immunol 4:43–52CrossRefPubMed
35.
go back to reference Navarro S, Cossalter G, Chiavaroli C et al (2011) The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 4:53–65CrossRefPubMed Navarro S, Cossalter G, Chiavaroli C et al (2011) The oral administration of bacterial extracts prevents asthma via the recruitment of regulatory T cells to the airways. Mucosal Immunol 4:53–65CrossRefPubMed
36.
go back to reference Fu R, Li J, Zhong H, Yu D et al (2014) Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3β-related T regulatory cell insufficiency. PLoS One 9(3):e92912CrossRefPubMedPubMedCentral Fu R, Li J, Zhong H, Yu D et al (2014) Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3β-related T regulatory cell insufficiency. PLoS One 9(3):e92912CrossRefPubMedPubMedCentral
Metadata
Title
The Immunotherapeutic Role of Bacterial Lysates in a Mouse Model of Asthma
Authors
Chentao Liu
Rong Huang
Rujie Yao
Aimei Yang
Publication date
01-10-2017
Publisher
Springer US
Published in
Lung / Issue 5/2017
Print ISSN: 0341-2040
Electronic ISSN: 1432-1750
DOI
https://doi.org/10.1007/s00408-017-0003-8

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