Interleukin-6 Stimulates Coagulation, not Fibrinolysis, in Humans

Stouthard, J.M.L.; Levi, Marcel; Hack, C. E.; Veenhof, C. H. N.; Romijn, Hans A.; Sauerwein, Hans P.; Poll, Tom van der

doi:10.1055/s-0038-1650653

Cited by 260 publications

(192 citation statements)

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“…21,42 High concentrations of inflammatory cytokines are related to an increased risk of thromboembolic complications. 43,44 Actually, it is becoming increasingly evident that anticoagulants, particularly natural anticoagulants, can limit the inflammatory-induced derangement in the coagulation. 45 AT-III, which is synthesized in the liver, is known to play an important role in the anticoagulant system by preventing intravascular thrombin formation and inhibiting coagulation by downregulating procoagulant activities.…”

Section: Discussionmentioning

confidence: 99%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

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Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response. The human body reacts to surgical stimuli through various systemic responses including the endocrine, metabolic, coagulation, and immune systems. However, extended damage may result in an exaggerated systemic response with an overwhelming activation of immune cells and the release of various mediators of stress. [1][2][3] The systemic reaction to the operation is considered to be equivalent to the systemic inflammation response syndrome, mainly caused by cytokine networks. 4,5 Raised levels of inflammatory cytokines have been related to higher postoperative mortality and morbidity rates. 2,3,6 Therefore, increased attention has evolved toward modulating potentially deleterious inflammatory response to the operation.The anti-inflammatory and immune modulating effects of steroids have been known for decades and have found extensive therapeutic use in a wide range of diseases in which inflammatory responses play major role. 7,8 Several trials have investigated the benefits of administering corticosteroids as a modulator of cytokine response in patients undergoing elective cardiothoracic or gastrointestinal surgery, as well as in cases of septic shock, suggesting that several aspects of the surgical stress responses, organ dysfunction, and postAbbreviations: POD, postoperative day; ALT, alanine aminotr...

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Section: Discussionmentioning

confidence: 99%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

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“…The associations of percent FAs and IL-6 need also to be interpreted in the context of the atherosclerotic process. It is well known that inflammation in the vessel wall plays an essential part in the initiation and progression of atherosclerosis (27)(28)(29). Damage to the vessel wall leads to endothelial cell disruption, resulting in exposure of the underlying vascular smooth muscle cells.…”

Section: Ferná Ndez-real and Associatesmentioning

confidence: 99%

Insulin Resistance, Inflammation, and Serum Fatty Acid Composition

Fernández-Real¹,

et al. 2003

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OBJECTIVE -Fatty acids (FAs) have been involved in the development of chronic inflammatory conditions such as insulin resistance and obesity. However, the relation among insulin resistance, obesity, inflammatory activity (circulating interleukin [IL]-6) and dietary FAs has been scarcely studied in otherwise healthy subjects.RESEARCH DESIGN AND METHODS -We aimed to study these interactions in 123 overweight (BMI 26.9 Ϯ 2.4 kg/m 2 [means Ϯ SD]) subjects and 109 lean (BMI 21.7 Ϯ 1.7 kg/m 2 , P Ͻ 0.000001) subjects. IL-6 was measured by immunoassay and FA by gas liquid cromatography.RESULTS -The percentage of saturated FAs (r ϭ 0.30, P ϭ 0.01) and -6 FAs (r ϭ Ϫ0.32, P ϭ 0.001) were significantly associated with circulating IL-6, whereas the percentage of -3 FAs correlated negatively with C-reactive protein in overweight subjects (P ϭ 0.04). Saturated-to--3 and saturated-to--6 FA ratios were significantly and positively associated with C-reactive protein (P Ͻ 0.0001) and IL-6 (P Ͻ 0.001), respectively. In contrast, none of these associations reached statistical significance in lean subjects. Those subjects in the most insulin-sensitive quintile (homeostasis model assessment value) showed a significantly higher percentage of linoleic acid (C18:2 6) (P ϭ 0.03) and a significantly lower level of araquidic (C20:0) (P ϭ 0.04), behenic (C22:0) (P ϭ 0.009), lignoceric (C24:0) (P ϭ 0.02), and nervonic (C24:1 9) (P ϭ 0.001) FAs than the remaining subjects. In parallel, the most insulin-sensitive subjects showed significantly decreased C-reactive protein (P ϭ 0.03). Serum C-reactive protein was significantly associated with percent linoleic acid and eicosapentaenoic acid in nonsmoking men (P ϭ 0.03 and P ϭ 0.04, respectively) and with docosahexaenoic acid in nonsmoking women (r ϭ Ϫ0.46, P Ͻ 0.0001). We constructed a multivariant regression analysis to predict circulating IL-6. Age, BMI, waist-to-hip ratio (WHR), smoking status, and the relation of saturated to -6 or saturated to -3 FAs were considered as independent variables separately in men and women. In overweight men, the ratio of saturated to -3 FAs (P ϭ 0.01), but not age, sex, BMI, WHR, or smoking status, independently contributed to 17% of IL-6 variance. In lean men, smoking status (P ϭ 0.02), but not the remaining variables, contributed to 8% of IL-6 variance.CONCLUSIONS -Dietary FAs (as inferred from plasma FA concentration) seem to be linked to inflammatory activity in overweight subjects and in subjects with insulin resistance. Being overweight modulates the relation of FAs to inflammatory markers. Diabetes Care 26:1362-1368, 2003I nsulin resistance is increasingly viewed as a chronic inflammatory disease (1). Different cytokines and chemical messengers constitute the main regulators of this inflammatory process, achieving biological effects individually as well as in association with each other. Interleukin (IL)-6 is a proinflammatory cytokine produced by many different cell types, including immune cells and adipose tissue (2,3). The major effects of IL-6 take pl...

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“…[11][12][13] Tumor necrosis factor-␣ and IL-6 were found to be related to the activation of blood coagulation, and IL-6 is a well known inducer of acute-phase proteins. [14][15][16] The signal transduction associated with IL-6 can be triggered by this cytokine complexed to its soluble receptor (IL-6sR), as well as to the one anchored to the cytoplasmic membrane. 17 Interleukin-8 is a chemokine from the C-X-C subfamily with potent neutrophil chemotactic and activating activity.…”

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confidence: 99%