Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated levels of soluble cell adhesion molecules (sCAMs), inflammatory cytokines and C-reactive protein (CRP) have been associated with atherosclerotic disease states. The aim of the present study was to evaluate whether circulating levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), E- and P-selectin were significantly elevated in patients with coronary heart disease (CHD) compared with healthy controls, and to study possible associations between these sCAMs, tumour necrosis factor alpha (TNFalpha). interleukin-6 (IL-6), CRP and major CHD risk factors. The study included 193 patients in various stages of CHD and 193 matched controls. To evaluate any possible influence of acute phase reaction, reinvestigation was performed after 6 months. After adjustment for major CHD risk factors, sVCAM-1, sICAM-1, P-selectin, IL-6 and CRP remained significantly elevated in the CHD patients (p for all <0.001). In multivariate analysis sVCAM-1 was predicted by age (p=0.015), sICAM-1 by smoking (p<0.001) and total cholesterol (p=0.026), E-selectin by body mass index (BMI) (p=0.004) and P-selectin by male gender (p=0.015). TNFalpha significantly predicted sICAM-1 and E-selectin levels, while IL-6 predicted CRP but none of the sCAMs measured. This might indicate that TNFalpha, but not IL-6, plays a major role in the regulation of sCAM levels in vivo.
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PMID:Increased levels of markers of vascular inflammation in patients with coronary heart disease. 1200 14

Infectious agents are possible stimulators of inflammation in atherogenesis. The aim of this study was to investigate if Chlamydia pneumoniae and Helicobacter pylori were associated with elevated levels of tumor necrosis factor alpha (TNFalpha) and interleukin-6 in coronary heart disease (CHD) patients (n=193) and age- and sex-matched controls (n=193) as markers of increased inflammatory activity. C reactive protein (CRP) and fibrinogen were also included. Serologic status towards the two bacteria was measured and levels of the inflammatory markers were compared between seropositives and seronegatives, each study group being evaluated separately. In CHD patients Chlamydia lipopolysaccharide (LPS) IgA seropositivity predicted elevated TNFalpha levels (P=0.009), still statistically significant after adjustment for traditional cardiovascular risk factors (P=0.005). Chlamydia LPS IgG seropositivity independently predicted fibrinogen levels in CHD patients (P=0.028), while no association between serology and inflammatory markers were observed among controls. H. pylori seropositivity alone was not associated with any increase in the inflammatory markers in any of the two groups. However, in CHD patients seropositivity to both agents predicted higher levels of TNFalpha (P=0.041), CRP (P=0.037) and fibrinogen (P=0.001) compared to double seronegativity. We conclude that C. pneumoniae LPS seropositivity may contribute to increased vascular inflammation in CHD patients, possibly even more pronounced when present in combination with H. pylori seropositivity.
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PMID:Positive Chlamydia pneumoniae serology is associated with elevated levels of tumor necrosis factor alpha in patients with coronary heart disease. 1211 4

High cholesterol is a well-established risk factor of myocardial infarction (MI). Since monocytes play a pivotal role in the development of atherosclerosis, one might anticipate that their functional properties are very important in relation to MI. In the present study, we have explored how the lipopolysaccharide (LPS)-induced reactivity of monocytes in whole blood in vitro relates to the serum lipid profile of healthy subjects with a history of MI or cancer in their close family. Twenty of the 54 subjects (of the total 266 test subjects) in the MI families had moderately high cholesterol (7.1-10.2 mmol/l), whereas 34 had normal cholesterol. Nineteen of the normocholesterol individuals had hyperactive monocytes (high responders), whereas 15 had monocytes responding normally. Two of the 20 subjects in the high cholesterol group had hyperactive monocytes. LPS-induced tissue factor, tumour necrosis factor-alpha and interleukin-6 were on the average three to four times higher in the normocholesterol group compared with the moderately hypercholesterol group, and hence no positive correlation was found between hyperactive monocytes and cholesterol. The 42 subjects in the families with cancer had normal cholesterol, and two of these subjects had very high LPS-induced tissue factor, tumour necrosis factor-alpha and interleukin-6, whereas eight of the 170 subjects without MI or cancer in their family were high responders. This further substantiates the notion that moderately high cholesterol is not associated with enhanced monocyte activation in whole blood. Hyperactive peripheral blood monocytes are suggested to be associated with a significant risk factor in developing coronary heart disease.
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PMID:Cellular activation responses in blood in relation to lipid pattern: healthy men and women in families with myocardial infarction or cancer. 1213 67

Despite mounting evidence that psychiatric depression heightens risk for cardiac morbidity and mortality, little is known about the mechanisms responsible for this association. The present study examined the relation between depression and the expression of inflammatory risk markers implicated in the pathogenesis of coronary heart disease (CHD). One hundred adults were enrolled (68% women, 48% Caucasian, 48% African-American, mean age 30 +/- 2 years). Fifty subjects met the diagnostic criteria for clinical depression; the remaining 50 were demographically matched controls with no history of psychiatric illness. All subjects were in excellent health, defined as having no acute infectious disease, chronic medical illness, or regular medication regimen aside from oral contraceptives. The depressed subjects exhibited significantly higher levels of the inflammatory markers C-reactive protein (3.5 +/- 0.5 vs 2.5 +/- 5 mg/L, p = 0.04) and interleukin-6 (3.0 +/- 0.3 vs 1.9 +/- 0.2 pg/ml, p = 0.007) compared with control subjects. Mediational analyses aimed at identifying the pathways contributing to this association revealed that neither cigarette smoking nor subclinical infection with cytomegalovirus or Chlamydia pneumoniae had been responsible. However, depressed subjects exhibited greater body mass than control subjects, and analyses were consistent with adiposity accounting for a portion of the relation between clinical depression and increased expression of inflammatory markers. These findings indicate that in otherwise healthy adults, depression is associated with heightened expression of inflammatory markers implicated in the pathogenesis of CHD. Increased body mass appears to be partially, although not completely, responsible for this relation.
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PMID:Clinical depression and inflammatory risk markers for coronary heart disease. 1248 34

Socioeconomic status is a major determinant of coronary heart disease (CHD). Proinflammatory cytokines are implicated in the etiology of CHD, and are also sensitive to emotional stress. We hypothesised that concentration of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 receptor antagonist (IL-1Ra) would be inversely related to socioeconomic status, and that cytokine responses to stress would be associated with SES. One hundred and twenty-five middle-aged men and 105 women from the Whitehall II epidemiological cohort were tested, and socioeconomic status was indexed by grade of employment, with participants divided into high, intermediate, and low status groups. Plasma concentrations at rest of TNF-alpha, IL-1Ra, and IL-6 (women only) were associated with socioeconomic status, with lower levels in the high status group, but the effect was non-linear. There was no relationship between socioeconomic status and cytokine responses to stress, but sex differences were observed, with men showing greater TNF-alpha, and women greater IL-6 and IL-1Ra increases. The role of inflammatory cytokines in mediating psychosocial influences on CHD is discussed.
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PMID:Inflammatory cytokines, socioeconomic status, and acute stress responsivity. 1248 May 6

Abnormalities in coagulation and haemostasis represent a well-known link between obesity and thrombosis (both arterial and venous). Several studies have shown that obese patients have higher plasma concentrations of all pro-thrombotic factors (fibrinogen, vonWillebrand factor (vWF), and factor VII), as compared to non-obese controls, with a positive association with central fat. Similarly, plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be higher in obese patients as compared to non-obese controls and to be directly correlated with visceral fat. Furthermore, obesity is characterized by higher plasma concentrations of anti-thrombotic factors, such as tissue-type plasminogen activator (t-PA) and protein C, as compared to non-obese controls, the increase in these factors being likely to represent a protective response partly counteracting the increase in pro-thrombotic factors. The issue of whether adipose tissue contributes directly to plasma PAI-1, its products stimulating other cells to produce PAI-1, or whether it primarily contributes indirectly has not yet been resolved. It has been proposed that the secretion of interleukin-6 (IL-6) by adipose tissue, combined with the actions of adipose tissue-expressed TNF-alpha in obesity, could underlie the association of insulin resistance with endothelial dysfunction, coagulopathy, and coronary heart disease. The role of leptin in impairing haemostasis and promoting thrombosis has been recently reported. Finally, some hormonal abnormalities (androgen, F, catecholamines) associated with the accumulation of body fat may contribute to the impairment of coagulative pathway in obesity. As to intervention strategies, dietary (i.e., low-fat high-fiber diet) and lifestyle (i.e., physical activity) measures have been demonstrated to be effective in improving the obesity-associated pro-thrombotic risk profile.
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PMID:Coagulation and fibrinolysis abnormalities in obesity. 1250 53

Coronary heart disease (CHD) is one of the main leading causes of death worldwide. CHD is a complex condition resulting from numerous gene-gene and gene-environment interactions. A large number of candidate genes exist. We review the evidence for the role of apolipoprotein E, lipoprotein lipase and interleukin-6 in CHD and their interaction with smoking (an environmental risk). The main objective of genetic research into CHD is to provide a complete risk assessment, complementing the well-studied traditional clinical and biochemical risk factors. Unravelling the role that functional gene polymorphisms play in determining risk, and in determining the levels of intermediate phenotypes is crucial to our understanding of the key metabolic pathways and physiology not only in the diseased, but also in the disease-free state. The identification of new molecules (implicated in the relevant metabolic pathways) may subsequently lead to potential targets for therapeutic intervention. Improving our molecular understanding may also lead to the development of improved diagnostics. Sequencing of the entire genome is now a reality. Advances in technology, such as the development of "gene chips" may allow us to study 100 000 genes at a time on a single chip. Such advances will amplify the power available to us in the realms of research into genetic physiology and interaction with environmental stimuli. The insights that these novel approaches may yield are eagerly awaited.
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PMID:The molecular genetics of cardiovascular disease: clinical implications. 1254 51

Despite mounting evidence that depression increases risk for cardiovascular morbidity and mortality, little is known about the mechanisms responsible for this association. The current study examined the inter-relationships between depression, adiposity, and inflammatory molecules implicated in the pathogenesis of coronary heart disease. One hundred adults were enrolled. Half were clinically depressed; the others were matched controls with no history of psychiatric illness. All subjects were in excellent health, defined as having no acute infectious disease, chronic medical illness, or prescribed medication regimen. Structural equation modeling yielded support for a model in which depressive symptoms promote weight accumulation, which in turn activates an inflammatory response through two distinct pathways: expanded adipose tissue release of interleukin-6 and leptin-induced upregulation of interleukin-6 release by white blood cells (CFI =.99; NNFI =.99; RMSEA =.05). It did not support a sickness behavior model in which the inflammatory molecules arising from expanded adipose tissue promote depressive symptoms.
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PMID:Pathways linking depression, adiposity, and inflammatory markers in healthy young adults. 1283 30

Coronary heart disease secondary to atherosclerosis is still the leading cause of death in the US. Animal models used for elucidating the pathogenesis of this disease primarily involve rabbits and pigs. Previous studies from this laboratory have demonstrated intraperitoneal injections of poloxamer 407 (P-407) in both male and female mice will lead to hyperlipidemia and atherosclerosis, suggesting the use of this polymer to develop a mouse model of atherosclerosis. In order to understand the mechanism of P-407-induced hyperlipidemia and vascular lesion formation, we evaluated the direct effects of P-407 on endothelial cell and macrophage functions in vitro, and its in vivo effects on the oxidation of circulating lipids following long-term (4 month) administration. Our results demonstrated that incubation of P-407 with human umbilical vein endothelial cells in culture did not influence either cell proliferation or interleukin-6 and interleukin-8 production over a concentration range of 0-40 microM. In addition, nitric oxide production by macrophages was not affected by P-407 over a concentration range of 0-20 microM. Finally, we demonstrated that while P-407 could not induce the oxidation of LDL-C in vitro, long-term (4 month) administration of P-407 in mice resulted in elevated levels of oxidized lipids in the plasma. Thus, it is suggested that the formation of atherosclerotic lesions in this mouse model of atherosclerosis does not result from either direct stimulation of endothelial cells or macrophage activation by P-407. Instead, these data would support the premise that oxidation of lipids (perhaps low-density lipoprotein cholesterol) by an indirect mechanism following injection of P-407 may represent one of the mechanisms responsible for atheroma formation.
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PMID:Poloxamer 407-induced atherosclerosis in mice appears to be due to lipid derangements and not due to its direct effects on endothelial cells and macrophages. 1285 98

Recent advances in basic science have shown that atherosclerosis should be considered as a chronic inflammatory process, and that a pivotal role of inflammation is evident from initiation through progression and complication of atherosclerosis. In the past few years many studies have examined the potential for biochemical markers of inflammation to act as predictors of coronary heart disease (CHD) risk in a variety of clinical settings. Several large, prospective epidemiological studies have shown consistently that C-reactive protein (CRP) and interleukin-6 (IL-6) plasma levels are strong independent predictors of risk of future cardiovascular events, both in patients with a history of CHD and in apparently healthy subjects. These molecules could be useful to complement traditional risk factors, as well as to identify new categories of subjects prone to atherosclerosis development. An intriguing question is whether these inflammatory molecules simply represent sensitive markers of systemic inflammation or if they actively contribute to atherosclerotic lesion formation and instability. In this paper we will review the evidence concerning the cardiovascular prognostic value and the potential direct involvement of CRP and IL-6 in atherogenesis.
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PMID:C-reactive protein and interleukin-6 in vascular disease: culprits or passive bystanders? 1450 81


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