Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Biphasic Increase of Pro-inflammatory Cytokines in Mice Lung after Irradiation

방사선 조사 후 흰 쥐의 폐에서 염증성 Cytokine의 발현 양상

  • Choi, Yun Jung (Department of Internal Medicine, Korea Cancer Center Hospital) ;
  • Rho, Jing Kyung (Department of Internal Medicine, Korea Cancer Center Hospital) ;
  • Jang, Won Seok (Department of Laboratory of Pathology, Korea Cancer Center Hospital) ;
  • Lee, Seon Joo (Department of Laboratory of Pathology, Korea Cancer Center Hospital) ;
  • Lee, Seung Sook (Department of Laboratory of Pathology, Korea Cancer Center Hospital) ;
  • Koh, Jae Soo (Department of Laboratory of Pathology, Korea Cancer Center Hospital) ;
  • Kim, Jae Yeol (Department of Internal Medicine, College of Medicine, Chung-Ang University) ;
  • Kim, Hye-Ryoun (Department of Internal Medicine, Korea Cancer Center Hospital) ;
  • Kim, Cheol Hyeon (Department of Internal Medicine, Korea Cancer Center Hospital) ;
  • Lee, Jae Cheol (Department of Internal Medicine, Korea Cancer Center Hospital)
  • 최윤정 (한국원자력의학원 내과) ;
  • 노진경 (한국원자력의학원 내과) ;
  • 장원석 (한국원자력의학원 실험병리학연구실) ;
  • 이선주 (한국원자력의학원 실험병리학연구실) ;
  • 이승숙 (한국원자력의학원 실험병리학연구실) ;
  • 고재수 (한국원자력의학원 실험병리학연구실) ;
  • 김재열 (중앙대학교 의과대학 내과학교실) ;
  • 김혜련 (한국원자력의학원 내과) ;
  • 김철현 (한국원자력의학원 내과) ;
  • 이재철 (한국원자력의학원 내과)
  • Received : 2009.06.04
  • Accepted : 2009.07.07
  • Published : 2009.07.30
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Abstract

Background: The pathophysiologic mechanisms of radiation-induced lung injury should be elucidated to enhance the therapeutic efficacy of radiotherapy and to manage patients exposed to serious radiation by accident. It has been suggested that pro-inflammatory cytokines play an important role in radiation-induced effect on the lung. This study was aimed to investigate changes in pro-inflammatory cytokines such as TNF-$\alpha$, MIP-2, IL-1$\beta$ and HMGB1, a newly recognized inflammatory mediator. Methods: The chests of BALB/c mice were selectively irradiated with single fraction of 20 Gy and then sacrificed at indicated times. Pathologic changes in the lung were examined after H&E staining. The expression level of pro-inflammatory cytokines was evaluated by ELISA kits in lung homogenate and in serum. Results: Radiation induced inflammatory changes and mild fibrosis in lung. Biphasic increase of TNF-$\alpha$ and IL-1$\beta$ was found in lung homogenate at 4 hours and at 3 weeks after radiation. The elevation in the second phase tended to be more intense. However, there was no similar change in serum. MIP-2 level was slightly increased in lung homogenate at 4 hours, but not at 3 weeks. HMGB1 was increased at 3 weeks in serum while there was no significant change in lung homogenate. Conclusion: Radiation induced a biphasic increase in TNF-$\alpha$ and IL-1$\beta$. The effective control of second phase cytokine elevation should contribute to preventing severe lung fibrosis caused by radiation.

연구배경: 방사선치료 효율의 증가와 방사선 피폭 환자의 치료에 있어 방사선으로 인한 폐 손상의 기전을 잘 파악하는 것이 무엇보다 중요한 일이다. 최근 염증성 cytokine의 활성화가 초기 방사선 폐렴뿐만 아니라 후기에 생기는 폐 섬유화에도 기여하고 있다는 보고들이 많이 나오고 있다. 저자들은 염증성 cytokine의 역할을 알아보기 위하여 방사선 후 흰 쥐의 폐와 혈청에서 이들의 변화를 관찰하였다. 방 법: 90마리의 흰 쥐 폐에 20 Gy의 방사선을 조사한 후 정해진 시간에 폐를 적출하여 병리학적 소견을 관찰하였다. 동시에 혈청과 lung homogenate에서 ELISA kit를 이용하여 염증성 cytokine의 변화를 조사하였다. 결 과: 방사선 조사 후 조직에서 염증세포의 침윤이 증가하고 시간이 지남에 따라 폐 섬유화가 생기는 것을 확인할 수 있었다. TNF-$\alpha$와 IL-1$\beta$는 4시간과 3주째 lung homogenate에서 증가하였는데 3주째 더 많이 증가하는 양상을 보여 주었다. 하지만 혈청에서의 변화는 뚜렷하지 않았다. MIP-2의 경우에는 4시간에 lung homogenate에서만 증가한 반면 HMGB1은 3주째 혈청에서만 증가하는 것을 알 수 있었다. 결 론: 방사선 조사 후 TNF-$\alpha$와 IL-1$\beta$ 등의 염증성 cytokine들이 biphasic expression하는 것을 보여 주었다. 후기 염증성 cytokine들의 증가를 효과적으로 억제할 수 있는 방법이 모색되어야 할 것으로 생각되고 이는 폐 섬유화로 진행하는 만성 합병증을 예방하는 데 기여할 것으로 판단된다.

Keywords

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