Journal of asthma, allergy and clinical immunology (천식및알레르기)

The Korean Academy of Asthma, Allergy and Clinical Immunology (대한천식알레르기학회)
권호 표지

Effects of Bacillus Calmette-Guerin (BCG) Vaccination according to Time Point of Administration on Asthma in a Murine Model

천식 마우스 모델에서 BCG백신의 투여시기에 따른 알레르기 염증반응 억제효과

  • Kim, Young-Joon (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Ha-Jung (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kang, Mi-Jin (Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kwon, Ji-Won (Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Seo, Ju-Hee (Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Byoung-Ju (Department of Pediatrics, Inje University, Haeundae Paik Hospital) ;
  • Yu, Jin-Ho (Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Hong, Soo-Jong (Department of Pediatrics, Childhood Asthma Atopy Center, Asan Medical Center, University of Ulsan College of Medicine)
  • 김영준 (울산대학교 의과대학 서울아산병원 아산생명과학연구소) ;
  • 김하정 (울산대학교 의과대학 서울아산병원 아산생명과학연구소) ;
  • 강미진 (울산대학교 의과대학 서울아산병원 아산생명과학연구소) ;
  • 권지원 (울산대학교 의과대학 서울아산병원 소아청소년과 소아천식아토피센터) ;
  • 서주희 (울산대학교 의과대학 서울아산병원 소아청소년과 소아천식아토피센터) ;
  • 김병주 (인제대학교 의과대학 해운대백병원 소아과학교실) ;
  • 유진호 (울산대학교 의과대학 서울아산병원 소아청소년과 소아천식아토피센터) ;
  • 홍수종 (울산대학교 의과대학 서울아산병원 소아청소년과 소아천식아토피센터)
  • Received : 2010.08.30
  • Accepted : 2010.09.29
  • Published : 2010.12.25
⟨ Previous Next ⟩

Abstract

Background: Asthma is a chronic allergic disease characterized by the infiltration of eosinophils into the airway and lung. Bacille Calmette-Guerin (BCG) has been reported to be beneficial to inhibit allergic inflammation in an animal asthma model. Objective: The aims of the study were to investigate the efficacy of BCG according to the time point of administration on asthma in a murine model. Method: BALB/c mice were treated with BCG ($1{\times}10^6$ CFUs) before sensitization (-5 days) or after sensitization (+12 days) in asthma-induced BALB/c mice by ovalbumin (OVA) sensitization. Bronchial hyperresponsiveness (BHR), influx of inflammatory cells in bronchoalveolar lavage (BAL) fluid, histopathological changes in the lung and systemic immune responses were assessed. Result: The administration of BCG before and after sensitization suppressed asthmatic responses, including BHR, OVA-specific immunoglobulin E (IgE) production, percentage of eosinophils in BALF and pulmonary eosinophilic inflammation in the murine model compared to the control group. However, total IgE, total cell count and OVA-IgG1 were significantly suppressed by BCG before sensitization only. Conclusion: BCG vaccinations, regardless of administration time point, suppressed asthmatic responses in mice. The mechanism of effect of BCG before sensitization is thought to be balance Th1/Th2 immune responses, but, that of BCG after sensitization may be different from BCG before sensitization.

Keywords

Acknowledgement

Supported by : 보건복지가족부

References

  1. Walker C, Bode E, Boer L, Hansel T, Blaser K, Virchow J. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Resp Dis 1992;146:109-15 https://doi.org/10.1164/ajrccm/146.1.109
  2. Wang JM, Rambaldi A, Biondi A, Chen ZG, Sanderson CJ, Montovani A. Recombinant human interleukin-5 is a selective eosinophil chemoattractant. Eur J Immunol 1989;19:701-5 https://doi.org/10.1002/eji.1830190420
  3. Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med 2006;355:2226-35 https://doi.org/10.1056/NEJMra054308
  4. Hong SJ, Ahn KM, Lee SY, Kim KE. The prevalences of asthma and allergic diseases in Korean children. Korean J Pediatr 2008; 51:343-50 https://doi.org/10.3345/kjp.2008.51.4.343
  5. Lee SI. Prevalence of childhood asthma in Korea: international study of asthma and allergies in childhood. Allergy Asthma Immunol Res 2010;2:61-4 https://doi.org/10.4168/aair.2010.2.2.61
  6. Strachan DP. Hay fever, hygiene and household size. Br Med J 1989;299:1259-60 https://doi.org/10.1136/bmj.299.6710.1259
  7. Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, Maisch S, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 2001;358: 1129-33 https://doi.org/10.1016/S0140-6736(01)06252-3
  8. Shirakawa T, Enomoto T, Sihimazu S, Hopkin JM. The inverse association between tuberculin responses and atopic disorder. Science 1996;275:77-9
  9. Hopfenspirger MT, Agrawal DK. Airway hyperresponsiveness, late allergic response, and eosinophilia are reversed with mycobacterial antigens in ovalbumin-presensitized mice. J Immunol 2002; 168:2516-22 https://doi.org/10.4049/jimmunol.168.5.2516
  10. Oliveira FH, Sarinho SW, Montenegro S, Neuenschwander C, Queiroz R, Medeiros D, et al. Production of interferon gamma in asthmatic patients with small bacille Calmette-Guerin scars: a pilot study. Allergy Asthma Proc 2006;27:516-22 https://doi.org/10.2500/aap.2006.27.2907
  11. Coffman RL, Seymour BW, Lebman DA, Hiraki DD, Christiansen JA, Shrader B, et al. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol Rev 1988;102:5-28 https://doi.org/10.1111/j.1600-065X.1988.tb00739.x
  12. Yang X, Fan Y, Wang S, Han X, Yang J, Bilenki L, et al. Mycobacterial infection inhibits established allergic inflammatory responses via alteration of cytokine production and vascular cell adhesion molecule-1 expression. Immunology 2002;105:336-43 https://doi.org/10.1046/j.0019-2805.2002.01377.x
  13. Nahori MA, Lagranderie M, Lefort J, Thouron F, Joseph D, Winter N, et al. Effects of Mycobacterium bovis BCG on the development of allergic inflammation and bronchial hyperresponsiveness in hyper-IgE BP2 mice vaccinated as newborns. Vaccine 2001;19:1484-95 https://doi.org/10.1016/S0264-410X(00)00345-5
  14. Shen H, Huang H, Wang J, Ye S, Li W, Wang K, et al. Neonatal vaccination with Bacillus Calmette-Guerin elicits longterm protection in mouse-allergic responses. Allergy 2008;63: 555-63 https://doi.org/10.1111/j.1398-9995.2008.01637.x
  15. Riffo-Vasquez Y, Spina D, Page C, Tormay P, Singh M, Henderson B, et al. Effect of Mycobacterium tuberculosis chaperonins on bronchial eosinophilia and hyper-responsiveness in a murine model of allergic inflammation. Clin Exp Allergy 2004; 34:712-9 https://doi.org/10.1111/j.1365-2222.2004.1931.x
  16. Tournoy KG, Kips JC, Schou C, Pauwels RA. Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness. Clin Exp Allergy 2000;30:79-85 https://doi.org/10.1046/j.1365-2222.2000.00772.x
  17. Erb KJ, Holloway JW, Sobeck A, Moll H, Le Gros G. Infection of mice with Mycobacterium bovis-BCG suppresses allergeninduced airway eosinophilia. J Exp Med 1998;187:561-9 https://doi.org/10.1084/jem.187.4.561
  18. Herz U, Gerhold K, Gruber C, Braun A, Wahn U, Renz H, et al. BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model. J Allergy Clin Immunol 1998;102:867-74 https://doi.org/10.1016/S0091-6749(98)70030-2
  19. Ahrens B, Gruber C, Rha RD, Freund T, Quarcoo D, Awagyan A, et al. BCG priming of dendritic cells enhances T regulatory and Th1 function and suppresses allergen-induced Th2 function in vitro and in vivo. Int Arch Allergy Immunol 2009;150:210-20 https://doi.org/10.1159/000222673
  20. Cundall M, Sun Y, Miranda C, Trudeau JB, Barnes S, Wenzel SE. Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids. J Allergy Clin Immunol 2003;112:1064-71 https://doi.org/10.1016/j.jaci.2003.08.013
  21. Zhang GS, Wang PL, Huang HQ, Shen HH. New insights into the effects of Mycobacterium bovis Bacillus Calmette-Gue'rin on asthma. Chin Med J 2009;122:577-83
  22. Yu JH, Kim HB, Lee SY, Park HY, Kim WK, Son MH, et al. The relationship between BCG vaccination and allergic diseases. Pediatr Allergy Respir Dis 2008;18:167-73