Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Serum Nitric Oxide and Tumor Necrosis Factor-α Levels in Patients with Kawasaki Disease

가와사키병 환아에서 면역글로불린 투여 전후의 혈중 Nitric Oxide와 Tumor Necrosis Factor-α에 대한 연구

  • Park, Ji Hye (Department of Pediatrics, College of Medicine, Ewha Womans University) ;
  • Shin, Jee Seon (Department of Pediatrics, College of Medicine, Ewha Womans University) ;
  • Hong, Young Mi (Department of Pediatrics, College of Medicine, Ewha Womans University)
  • 박지혜 (이화대학교 의과대학 소아과학교실) ;
  • 신지선 (이화대학교 의과대학 소아과학교실) ;
  • 홍영미 (이화대학교 의과대학 소아과학교실)
  • Received : 2005.01.30
  • Accepted : 2005.03.09
  • Published : 2005.07.15
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Abstract

Purpose : Kawasaki disease(KD) is a systemic panvasculitis that causes coronary artery lesions. KD is accompanied by immunoregulatory abnormalities. Nitric oxide(NO) can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells and high levels of NO may result in coronary artery lesions. We investigated tumor necrosis factor$(TNF)-{\alpha}$ and NO production before and after intravenous immunoglobulin(IVIG) therapy to study the roles of NO and $TNF-{\alpha}$ in KD with coronary artery lesions. Methods : Serum levels of NO and $TNF-{\alpha}$ were measured in 24 patients with KD(group I, eight patients with normal coronary artery; group II, 16 patients with coronary artery lesions) and 23 controls(group III, 13 afebrile controls; group IV, 10 febrile controls). Blood samples from each subject were drawn before and after IVIG therapy and in the convalescent stage. Serum concentrations of NO and $TNF-{\alpha}$ were measured by enzyme linked immuno sorbent assay. Results : The NO levels before IVIG therapy were significantly higher in group II than in group I, group III and group IV. After IVIG therapy the levels of NO were significantly higher in group I and group II than in group III. The $TNF-{\alpha}$ levels before IVIG therapy were significantly higher in group I and group II than in group III. The serum $TNF-{\alpha}$ and NO levels were higher before IVIG therapy and decreased through the convalescent stage in KD patients. In the acute stage of KD patients with coronary artery lesions, serum NO levels significantly correlated with white blood cells (r=0.43, P<0.05). Conclusion : The serum concentration levels of $TNF-{\alpha}$ and NO were abnormally high in KD patients and NO concentrations were statistically higher in the KD patients with coronary artery abnormalities than those without coronary abnormality during the early stage of the KD. These results suggest NO may be involved in the development of coronary artery lesions.

목 적 : 가와사키병은 면역 조절 인자의 이상을 동반하는 전신적 혈관염으로 관상동맥질환을 초래한다. NO는 혈관내 평활근의 granulocyte cyclase의 기전에 영향을 미쳐 혈관의 이완을 유발하는 역할을 하며 과다하게 분비될 경우 혈관의 변성을 초래하는 것으로 알려져 있다. 본 저자들은 가와사키병에서 NO와 $TNF-{\alpha}$의 혈중 농도를 측정하여 관상동맥질환 발생과 연관이 있는지 알아보기 위해 본 연구를 실시하였다. 방 법 : 가와사키병 환아 24명을 관상동맥 확장이 없는 군(1군)과 관상동맥 확장이 있는 군(2군)으로 분류하여 각 군의 임상 양상과 면역글로불린 투여 전과 후, 회복기에서의 NO, $TNF-{\alpha}$의 혈중 농도를 면역효소법(ELISA)으로 측정하여 비교하였다. 대조군으로는 같은 시기에 내원한 열이 없는 정상 대조군(3군) 13명과 열이 있는 대조군(4군) 10명으로 하였다. 결 과 : 면역글로불린 투여 전의 혈중 NO는 1군($13.2{\pm}5.7{\mu}mol/L$), 2군($20.4{\pm}10.7{\mu}mol/L$)과 4군($12.4{\pm}8.9{\mu}mol/L$)이 3군($3.1{\pm}1.4{\mu}mol/L$)보다 높았고 2군이 1군과 4군에 비해 유의하게 높았다(P<0.05). $TNF-{\alpha}$는 2군($858.4{\pm}934.0pg/mL$)에서 3군($8.7{\pm}2.3pg/mL$)과 4군($226.7{\pm}647.2pg/mL$)에 비해 유의하게 높았으며 1군($522.4{\pm}859.6pg/mL$)도 3군에 비해 높았다(P<0.05). 면역글로불린 투여 후 NO는 1군, 2군과 4군이 3군에 비해 유의하게 높았으며 $TNF-{\alpha}$는 각 군별로 유의한 차이가 없었다. 가와사키병 관상동맥 확장군과 비확장군 모두에 있어 NO와 $TNF-{\alpha}$의 혈중 농도가 면역글로불린 투여 전에 가장 높았고 면역글로불린 투여 후와 회복기로 갈수록 감소하였다. 또한 관상동맥 확장군에서 백혈구 수치와 혈청 NO는 유의한 양의 상관관계가 있었다(r=0.430). 결 론 : 가와사키병 환자에 있어 NO, $TNF-{\alpha}$의 혈중 농도가 유의하게 높았으며 NO의 농도가 관상동맥이 확장된 환자에서 비 확장군보다 의미있게 높은 것으로 보아 NO가 관상동맥질환에 관여할 것으로 생각한다.

Keywords

References

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