Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Preventive Effect of Allergic Inflammation by Induction of Oral Tolerance in a Mouse Model of Chronic Asthma

마우스 만성천식모델에서 경구면역관용 유도에 의한 알레르기 염증의 예방효과

  • Kim, Jin Sook (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Lee, Jung Mi (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Seung Joon (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Lee, Sook Young (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kwon, Soon Seog (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Young Kyoon (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Kim, Kwan Hyoung (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Moon, Hwa Sik (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Song, Jeong Sup (Department of Internal Medicine, The Catholic University of Korea College of Medicine) ;
  • Park, Sung Hak (Department of Internal Medicine, The Catholic University of Korea College of Medicine)
  • 김진숙 (가톨릭대학교 의과대학 내과학교실) ;
  • 이정미 (가톨릭대학교 의과대학 내과학교실) ;
  • 김승준 (가톨릭대학교 의과대학 내과학교실) ;
  • 이숙영 (가톨릭대학교 의과대학 내과학교실) ;
  • 권순석 (가톨릭대학교 의과대학 내과학교실) ;
  • 김영균 (가톨릭대학교 의과대학 내과학교실) ;
  • 김관형 (가톨릭대학교 의과대학 내과학교실) ;
  • 문화식 (가톨릭대학교 의과대학 내과학교실) ;
  • 송정섭 (가톨릭대학교 의과대학 내과학교실) ;
  • 박성학 (가톨릭대학교 의과대학 내과학교실)
  • Received : 2004.09.10
  • Accepted : 2004.09.23
  • Published : 2004.11.30
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Abstract

Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.

연구배경 : 경구면역관용 유도는 4주 이내의 급성천식모델에서 알레르기 염증반응을 효과적으로 억제하는 것으로 알려져 있다. 하지만 경구면역관용 유도가 4주 이상 지속되는 만성천식모델에서도 알레르기 염증반응을 효과적으로 억제할 수 있는 지에 대해서는 아직 불확실하다. 본 연구에서는 8주 동안 지속되는 만성천식모델을 이용하여 경구면역관용 유도가 알레르기 염증반응 및 기도재형성에 어떤 영향을 미치는 지를 관찰하였다. 방 법 : 5주된 암컷 BALB/c 마우스에 ovalbumin(OVA)을 복강 내로 투여하여 감작시킨 후, 6주 동안 주 2회 OVA를 반복 흡입시킴으로써 만성천식모델을 만들었다. 경구면역관용은 감작시키기 전에 OVA를 경구 투여함으로써 유도하였으며, 저용량 군(OVA 1 $mg/day{\times}6$일)과 고용량 군(OVA 25 $mg/day{\times}1$일)으로 나누었다. 기도과민성은 농도별 메타콜린 흡입에 따른 enhanced pause (penh) 값의 변화로 평가하였으며, 기관지폐포세척액 내의 염증세포수를 측정하고 IL-13, IFN-${\gamma}$ 농도 및 혈청 내 OVA 특이 IgE, IgG1, IgG2a 농도를 ELISA로 측정하였다. 기도재형성 정도는 폐조직의 PAS 및 Masson's trichrome 염색으로 관찰하였다. 결 과 : 경구면역관용군은 천식군에 비해 penh 값, 기관지폐포세척액 내의 염증세포 수, IL-13 및 IFN-${\gamma}$ 농도, 혈청 내의 OVA 특이 IgE, IgG1 및 IgG2a 농도, 폐조직 술잔세포의 과다형성, 기저막하부의 섬유화 정도가 유의하게 감소되었다 (P<0.05). 결 론 : 알레르기 기관지천식모델에서 경구면역관용 유도는 8주까지 장기적으로 기도과민성, 염증반응 및 기도재 형성을 억제하였으며, 그 기전에는 항원 특이 면역글로불린과 Th1 및 Th2 시토카인들에 대한 억제작용이 중요한 역할을 하는 것으로 추측되었다.

Keywords

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