생명과학회지 (Journal of Life Science)

  • 제18권11호
  • /
  • Pages.1551-1560
  • /
  • 2008
  • /
  • 1225-9918(pISSN)
  • /
  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
DOI QR코드

DOI QR Code

체외순환을 동반한 심장판막 수술 시 혈청 사이토카인 농도와 수술 후 결과와의 상관관계 분석

Analysis of the Correlations between the Serum Levels of Cytokines and Postoperative Outcomes in Valvular Heart Surgery with Cardiopulmonary Bypass

  • 문성민 (인제대학교 식의학생명공학대학 임상병리학과) ;
  • 김정락 (인제대학교 식의학생명공학대학 임상병리학과) ;
  • 김윤태 (서울의과학 연구소) ;
  • 최석철 (부산가톨릭대학교 보건과학대학 임상병리학과)
  • Moon, Seong-Min (Department of Biomedical Laboratory of Science, College of Smart Foods and Drugs, Inje University) ;
  • Ki, Chong-Rak (Department of Biomedical Laboratory of Science, College of Smart Foods and Drugs, Inje University) ;
  • Kim, Yun-Tae (Seoul Medical Science Institute (SMSI)) ;
  • Choi, Seok-Cheol (Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan)
  • 발행 : 2008.11.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

본 연구자들은 체외순환을 적용한 심장판막 수술 시 혈청사이토카인들의 변화와 여러 장기 표지자들과의 상관관계규명을 위해 전향적 연구를 실시하였다. 체외순환은 수술 동안 또는 수술 후 시기에 걸쳐 염증성 사이토카인(TNF-$\alpha$ 및 IL-6) 및 항염증성 사이토카인(IL-10)의 혈청 농도의 증가를 가져왔고 염증성 사이토카인의 증가에 따라 항염증성 사이토카인의 길항적 상승이 뒤 따랐다. 또한 심장수술 후 간, 신장, 심장 등 장기의 기능표지자들 역시 기준치보다 증가되었고 사이토카인들은 이러한 장기기능 표지자와 다양한 시기에 걸쳐 유의한 상관성을 보였다. 본 연구의 결과들은 심장판막수술 시 필연적으로 적용하는 체외순환이 염증성 사이토카인을 활성화시키기도 하지만 이의 상쇄를 위한 항염증성 사이토카인의 방출 역시 자극하며 이러한 사이토카인들은 수술 후 여러 장기의 기능에 직간접적으로 관여하여 장기 손상 혹은 장기보호의 역할을 함이 시사되었다.

Cytokines play a pivotal role in systemic inflammatory response following cardiac surgery with cardiopulmonary bypass (CPB). The purpose of this study was to investigate the perioperative changes in proinflammatory [tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6)] and antiinflammatory cytokines [interleukin-10 (IL-10)], and each correlation between the cytokines and other variables in valvular heart surgery with CPB. Serum IL-6 and IL-10 levels and leukocyte counts significantly increased following CPB. CPB caused hepatic, renal and myocardial dysfunctions. IL-6 levels had positive correlations with IL-10 levels at postoperative periods. TNF-$\alpha$ levels had correlations with leukocyte counts and myocardial marker levels at postoperative 24 hr (PO-24 h). Furthermore, IL-6 or IL-10 levels had positive correlations with other variable such as hepatic, renal or myocardial marker at postoperative periods. These results showed that balance between proinflammatory and antiinflammatory cytokines is maintained during cardiac surgery with CPB, and that these cytokines exert postoperatively inflammatory and antiinflammatory reactions.

키워드

참고문헌

  1. Bogdan, C., Y. Vodovotz and C. Nathan 1991. Macrophage deactivation by IL-10. J. Exp. Med. 174, 1549-1555. https://doi.org/10.1084/jem.174.6.1549
  2. Buttler, J., G. M. Rocker and S. Westaby. 1993. Inflammatory response to cardiopulmonary bypass. Ann. Thorac. Surg. 55, 553-559.
  3. Cain, B. S., D. R. Meldrum, and C. A. Dinarello. 1999. Tumor necrosis factor-alpha and interleukin-1 beta synergistically depress human myocardial function. Crit. Care. Med. 27, 1309-1318. https://doi.org/10.1097/00003246-199907000-00018
  4. Cremer, J., A. Haverich and H. G. 1996. Borst HG. Systemic inflammatory response after cardiac operations. Ann. Thorac. Surg. 61, 1714-1720. https://doi.org/10.1016/0003-4975(96)00055-0
  5. Finkel, M. S., C. V. Oddis, T. D. Jacob, S. C. Watkins, B. G. Hattler and R. L. 1992. Simmons. Negative inotropic effects cytokines on the heart mediated by nitric oxide. Science 257, 387-389. https://doi.org/10.1126/science.1631560
  6. Grunenfelder, J., G. Zund and A. Schoeberlein. 2000. Modified ultrafiltration lowers adhesion molecule and cytokine levels after cardiopulmonary bypass without clinical relevance in adults. Eur. J. Cardiothorac. Surg. 17, 77-83. https://doi.org/10.1016/S1010-7940(99)00355-3
  7. Gu, Y. J., W. Van Oeveren, C. Akkerman, P. W. Boonstra, R. J. Huyzen and C. R. H. Wildevuur. 1993. Heparin-coated circuits reduce the inflammatory response to cardiopulmonary bypass. Ann. Thorac. Surg. 55, 917-922. https://doi.org/10.1016/0003-4975(93)90117-Z
  8. Hauser, G. J., J. Ben-Ari and M. P. Colvin. 1998. Interleukin-6 levels in serum and lung lavage fluid of children undergoing open heart surgery correlated with postoperative morbidity. Intensive Care Med. 24, 481-486. https://doi.org/10.1007/s001340050600
  9. Hill, G. E., A. Alonso, J. R. Spurzem, A. H. Stammers and R. A. Robbins. 1995. Aprotinin and methylprednisolone equally blunt cardiopulmonary bypass-induced inflammation in humans. J. Thorac. Cardiovasc. Surg. 110, 1658-1662. https://doi.org/10.1016/S0022-5223(95)70027-7
  10. Hong, N. K., D. H. Lee, T. C. Jung, J. C., Lee and S. S. Han. 2000. Changes of IL-10 level in patients undergoing cardiopulmonary bypass. Korean Thorac. Cardiovasc. Surg. 33, 648-654.
  11. Hovels-Gurich, H., K. Schumacher, J. F. Vazquez-Jimenez, M. Qing, U. Huffneier, B. Buding, B. J. Messmer, G. V. Bernuth and M. C. Seghaye. 2002. Cytokine balance infants undergoing cardiac operation. Ann. Thorac. Surg. 73, 601-609. https://doi.org/10.1016/S0003-4975(01)03391-4
  12. Jeong, H. Y. Molecular biology of cytokine. 2002. pp. 73-85, World Science Press. Seoul, Korea.
  13. Krakauer, T. 1995. IL-10 inhibits the adhesion of leukocyte cells to IL-1-activated human endothelial cells. Immuno. Lett. 45, 61-65. https://doi.org/10.1016/0165-2478(94)00226-H
  14. Kukiella, G. L., C. W. Smith and A. M. Manning. 1995. Induction of interleukin-6 synthesis in myocardium: potential role in postperfusion inflammatory injury. Circulation 92, 1866-1875. https://doi.org/10.1161/01.CIR.92.7.1866
  15. Levy, J. H. and K. A. Tanaka. 2003. Inflammatory response to cardiopulmonary bypass. Ann. Thorac. Surg. 75, S715-S720. https://doi.org/10.1016/S0003-4975(02)04701-X
  16. Luster, A. D. 1998. Chemokines-chemotactic cytokines that mediate inflammation. New Eng. J. Med. 338, 457-470.
  17. Moore, K. W., A. Gorra, R. Waal Malefylt, P. Viera and T. R. Mosmann. 1993. Interleukin-10. Annu. Rev. Immunol. 11, 168-190.
  18. Opal, S. M. and V. A. De Palo. 2000. Anti-inflammatory cytokines. Chest 117, 1162-1172. https://doi.org/10.1378/chest.117.4.1162
  19. Ostrowski, K., C. Hermann, A. Bangash., P. Schjerling, J. N. Nielsen, and B. K. Pedersen. 1998. A trauma-like elevation of plasma cytokines in humans in response to treadmill running. J. Physiol. 513, 889-894. https://doi.org/10.1111/j.1469-7793.1998.889ba.x
  20. Ostrowski, K., T. Rohde, S. Asp, P, Schjerling and B. K. Pedersen. 1999. Pro-and anti-inflammatory cytokine balance in strenuous exercise in humans. J. Physiol. 515, 287-291. https://doi.org/10.1111/j.1469-7793.1999.287ad.x
  21. Ostrowski, K., Y. Rohde, M. Zacho, S. Asp and B. K. Pedersen. 1998. Evidence that interleukin-6 in produced in human skeletal muscle during prolonged running. J. Physiol. 508, 949-953. https://doi.org/10.1111/j.1469-7793.1998.949bp.x
  22. Park, K. H., S. C. Choi, I. Y. Han, K. L. Choi, K. J. Choi and K. H. Cho. 2000. Relationship between interleukin-6 production and inflammatory response during cardiopulmonary bypass. Korean Thorac. Cardiovasc. Surg. 33, 407-418.
  23. Schurr, U. P., G. Zund, S. P. Hoerstrup, J. Grunenfelder, F. E. Maly, P. R. Vogt and M. I. Turina. 2001. Preoperative administration of steroids: Influence on adhesion molecules and cytokine after cardiopulmonary bypass. Ann. Thorac. Surg. 72, 1316-1320. https://doi.org/10.1016/S0003-4975(01)03062-4
  24. Shottelius, A., M. W. Mayo, R. B. Sartor and A. S. Baldwin. 1999. Interleukin-10 signaling blocks inhibitor of kB kinase activity and nuclear factor kB DNA binding. J. Biol. Chem. 274, 31868-31874. https://doi.org/10.1074/jbc.274.45.31868
  25. Steinberg, J. B., D. P. Kapelanski, J. D. Olson and J. M. Weiler. 1993. Cytokine and complement levels in patients undergoing cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg. 106, 1008-1016.
  26. Steinberg, B. M., E. A. Grossi and D. S. Schwarz. 1995. Heparin bonding of bypass circuits reduces cytokine release during cardiopulmonary bypass. Ann. Thorac. Surg. 60, 525-529. https://doi.org/10.1016/0003-4975(95)00482-Z
  27. Stordeur, P. and M. Goldman. 1998. Interleukin-10 as a regulatory cytokine induced by cellular stress: molecular aspects. Int. Rev. Immunol. 16, 501-522. https://doi.org/10.3109/08830189809043006
  28. Strieter, R. M., S. L. Kunkel and R. C. Bone. 1993. Role of tumor necrosis factor-$\alpha$ in disease states and inflammation. Crit. Care. Med. 21(Suppl), S447-463. https://doi.org/10.1097/00003246-199303000-00024
  29. Van der Poll, T., J. Jansen, M. Levi and S. J. H. Van Deventer. 1994. Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees. J. Exp. Med. 180, 1985-1988. https://doi.org/10.1084/jem.180.5.1985
  30. Vary, T., S. Hazens, G. Maish and R. Cooney. 1998. TNF binding protein prevents hyperlactaemia and inactivation of PDH complex in skeletal muscle during sepsis. J. Surg. Res. 80, 44-51. https://doi.org/10.1006/jsre.1998.5324
  31. Vassalli, P. 1992. The pathophysiology of tumor necrosis factors. Annu. Rev. Immunol. 10, 411-452. https://doi.org/10.1146/annurev.iy.10.040192.002211
  32. Yang, Z., B. Zingarelli and C. Szabo. 2000. Crucial role of endogenous interleukin-10 production in myocardial ischemia/reperfusion injury. Circulation 101, 1019-1026. https://doi.org/10.1161/01.CIR.101.9.1019
  33. Zhang, Y., J. X. Lin, Y. K. Yip and J. Vilcek. 1989. Stimulation of interleukin-6 mRNA levels by tumor necrosis factor and interleukin-1. Ann. NY. Acad. Sci. 557, 548-549.