패혈증의 경과에 따른 혈중 스테로이드와 Nitric Oxide의 연관성 = Correlation of Nitric Oxide and Corticosteroids Along the Course of Sepsis

국문 초록 (Abstract)

연구배경: 패혈증에서 Nitric oxide 스테로이드 호르몬은 혈역학적 변화와 염증반응에 관여하는데 이 두 인자는 서로 상관성이 있는 것으로 알려지고 있다. 하지만 실제 환자에서 서로의 상관성이나 임상적 의의는 연구가 부족한 실정이다. 방법: 패혈증 환자 26예와 대조군 14예를 대상으로 혈중 총 NO와 혈중 코티졸 농도를 측정하였고 이어서 제 3, 5, 7병일에도 연속적으로 측정을 하였다. 결과: 패혈증 환자군에서 초기 혈중 코티졸 및 총 NO 농도는 대조군에 비하여 유의하게 증가하였고 경증 패혈증에 비하여 중증 패혈증 환자군에서 유의하게 높았다. 초기 혈중 총 NO의 농도는 APACHE II 점수, 정맥혈 lactate 농도와 상관성이 있었다. 패혈증의 시간의 경과에 따라 혈중 NO 농도는 제 1병일, 제 5병일, 제 7병일에 혈중 코티졸의 농도와 유의한 상관성이 있었다. 결론: 패혈증 환자들에서 혈중 NO와 코티졸 농도는 증가되어 있었으며, 경과에 따라 서로 유의한 상관성이 지속되었다. 상호작용기전에 대하여는 추가적인 연구가 필요할 것이다.

다국어 초록 (Multilingual Abstract)

Background: The nitric oxide (NO) released by inducible NO synthase (iNOS) plays an important role in the pathophysiology of sepsis. Corticosteroids also play a role in the hemodynamic and inflammatory reactions in sepsis. Both have been shown to have a relationship theoretically, but their correlation and clinical impacts have rarely been evaluated. Methods: 26 patients with sepsis and 14 healthy controls were enrolled in this study. The initial random plasma total NO and the serum cortisol levels were measured. The same measurements were serially carried out on the 3rd, 5th, and 7th days. Results: The initial total plasma levels of NO and cortisol were higher in the patients with sepsis than in the healthy controls. The total NO levels were higher in patients with severe sepsis than in the those with mild sepsis. There was a correlation between the total NO and cortisol level throughout the study. Conclusion: In patients with sepsis, the levels of plasma NO and cortisol were well correlated during the first week of sepsis, which suggests an interrelationship. However, the clinical and pathogenetic implications await further evaluation. (Tuberc Respir Dis 2007; 62: 308-313)

참고문헌 (Reference)

1 "iNOS gene expression modulates microvascular responsiveness in endotoxin- challenged mice" 87 : E18-E24, 2000

2 "The role of nitric oxide in sepsis:an overview" 43 : 275-288, 1999

3 "The pathogenesis of sepsis" 17 : 183-197, 1996

4 "Significance of corticosteroids and their relationship with other parameters in patients with sepsis" 61 : 631-640, 2006

5 "Septic shock" 365 : 63-78, 2005

6 "Role of nitric oxide in the vascular dysfunction of septic shock" 23 : 1025-1029, 1995

7 "Relationships of circulating nitrite/nitrate levels to severity and multiple organ dysfunction syndrome in systemic inflammatory response syndrome" 19 : 305-309, 2003

8 "Nitric oxide, sepsis and liver metabolism" 25 : 929-934, 1997

9 "Nitric oxide synthases: structure, function and inhibition" 357 : 593-615, 2001

10 "Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to catecholamines in septic rats" 264 : 660-3, 1993

11 "Nitric oxide plays a role in the regulation of adrenal blood flow and adrenocorticomedullary functions in the llama fetus" 544 : 267-276, 2002

12 "Nitric oxide in sepsis and endotoxaemia" 41S : 31-39, 1998

13 "Nitric oxide and shock" 43 : 277-348, 1997

14 "Nitric oxide (NO) production correlates with renal insufficiency and multiple organ dysfunction syndrome in severe sepsis" 22 : 1197-1202, 1996

15 "Multiple organ failure in septic shock" 216 : 209-237, 1996

16 "Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA" 196 : 1208-13, 1993

17 "L-arginine:nitric oxide pathway in endotoxemia and human septic shock" 23 : 253-258, 1995

18 "Inhibition of glucocorticoid receptor binding by nitric oxide in endotoxemic rats" 32 : 2304-2310, 2004

19 "Inhibition of glucocorticoid receptor binding by nitric oxide" 55 : 317-323, 1999

20 "Indices of nitric oxide synthesis and outcome in critically ill patients" 56 : 326-330, 2001

21 "Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide" 87 : 2593-7, 1990

22 "Glucocorticoids regulate inducible nitric oxide synthase by inhibiting tetrahydrobiopterin synthesis and L-arginine transport" 271 : 23928-23937, 1996

23 "Glucocorticoids inhibit the expression of an inducible nitric oxide synthase in vascular endothelial cells" 10043-7,

24 "Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide" 273 : 1972-1979, 1997

25 "Effects of nitric oxide in septic shock" 161 : 1781-1785, 2000

26 "Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock" 288 : 862-871, 2002

27 "Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone:an insight into endotoxin shock" 173 : 541-7, 1990

28 "Clinical biology of nitric oxide" 82 : 1598-1610, 1995

29 "Biochemical aspects of nitric oxide" 10 : 1627-1645, 2004

30 "Attenuation of the induction of nitric oxide synthase by endogenous glucocorticoids accounts for endotoxin tolerance in vivo" 91 : 271-5, 1994

31 "Association of microvascular leakage with induction of nitric oxide synthase:effects of nitric oxide synthase inhibitors in various organs" 283 : 47-53, 1995

32 "APACHE II:a severity of disease classification system" 13 : 818-29, 1985

33 "2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference" 31 : 1250-1256, 2003