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

Cilostazol, a novel oral phosphodiesterase inhibitor, has shown consistent improvement in exercise tolerance in patients with intermittent claudication (IC). In addition to this effect, cilostazol has previously been shown to have beneficial effects on the dyslipidemia, i.e., combination of high triglycerides with low high-density-lipoprotein cholesterol (HDL-C) levels. Interleukin-6 (IL-6) suppresses the activity of lipoprotein lipase, which modulates the metabolism of triglycerides and HDL-C. To determine whether a reduction of IL-6 contributes to the improvement of lipid profiles, we prospectively investigated the effect of cilostazol (n=16, 100 mg, twice daily) on the changes of lipid profiles and on the association with the changes of IL-6 compared with those of pentoxifylline (n=16, 400 mg, bid) in patients with IC. After eight weeks of administration of cilostazol to patients with IC, walking distances were increased, associated with a 29% decrease in plasma triglycerides and a 13% increase in HDL-C. No significant changes of lipid profiles in the pentoxifylline and placebo groups were observed although a similar improvement in walking distances was achieved in the pentoxifylline group. IL-6 levels were significantly reduced in patients receiving cilostazol as compared with those receiving placebo or pentoxifylline. The cilostazol-induced changes in the IL-6 were positively related to those of triglycerides in the cilostazol group (r=0.63, P<0.05) and negatively related to those of HDL-C (r=-0.55, P<0.05). These findings suggest that in addition to consistent improvement of exercise tolerance, cilostazol may improve lipid profiles by reducing IL-6 release. However, pentoxifylline did not affect lipid profiles although a similar improvement of maximal walking distance (MWD) was achieved.
Atherosclerosis 2001 Oct
PMID:Differential lipogenic effects of cilostazol and pentoxifylline in patients with intermittent claudication: potential role for interleukin-6. 1158 28

Inflammatory processes play a pivotal role in the pathogenesis of atherosclerosis and mediate many of the stages of atheroma development from initial leukocyte recruitment to eventual rupture of the unstable atherosclerotic plaque. Elevated plasma levels of several markers of the inflammatory cascade have been shown to predict future risk of plaque rupture. These markers include P-selectin, interleukin-6, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, and C-reactive protein (CRP). Produced in the liver in response to interleukin-6, CRP has emerged as the most powerful inflammatory marker of future cardiovascular risk. Initially considered an innocent bystander in the atherosclerotic process, recent evidence suggests that CRP may have direct proinflammatory effects. Numerous large-scale, prospective studies have found that elevated baseline levels of CRP are a strong independent predictor of future vascular risk. Furthermore, aspirin and statin therapy appear to be particularly effective among individuals with high CRP levels. The addition of CRP screening to traditional lipid testing has the potential to identify individuals at high risk for future cardiovascular events who may benefit from targeted preventive interventions.
 ...
PMID:Novel clinical markers of vascular wall inflammation. 1167 5

Evidence from a broad range of studies demonstrates that atherosclerosis is a chronic disease that, from its origins to its ultimate complications, involves inflammatory cells (T cells, monocytes, macrophages), inflammatory proteins (cytokines, chemokines), and inflammatory responses from vascular cells (endothelial cell expression of adhesion molecules). Investigators have identified a variety of proteins whose levels might predict cardiovascular risk. Of these candidates, C-reactive protein, tumor necrosis factor-alpha, and interleukin-6 have been most widely studied. There is also the prospect of inflammation as a therapeutic target, with investigators currently debating to what extent the decrease in cardiovascular risk seen with statins, angiotensin-converting enzyme inhibitors, and peroxisome proliferator-activated receptor ligands derives from changes in inflammatory parameters. These advances in basic and clinical science have placed us on a threshold of a new era in cardiovascular medicine.
 ...
PMID:Inflammatory pathways in atherosclerosis and acute coronary syndromes. 1169 13

The plasma level of interleukin-6 (IL-6) is elevated in patients with acute coronary syndromes and has prognostic value. Thrombin is a potent mitogen for vascular smooth muscle cells (VSMCs) and plays an important role in the progression of atherosclerosis. We examined the mechanism of thrombin-induced IL-6 expression in VSMCs. Thrombin induced IL-6 mRNA and protein expression in a dose-dependent manner. Pharmacological inhibition of extracellular signal-regulated protein kinase (ERK), p38 mitogen-activated protein kinase (MAPK), or epidermal growth factor receptor (EGF-R) suppressed the thrombin-induced IL-6 expression. Deletion and mutation analysis of the promoter region of the IL-6 gene by using luciferase as a reporter showed that the DNA segment between -228 and -150 bp containing the cAMP response element (CRE) site played a critical role. Thrombin also induced phosphorylation of CRE binding protein (CREB) in an ERK- and a p38 MAPK-dependent manner. Overexpression of the dominant-negative form of CREB inhibited thrombin-induced IL-6 mRNA expression. These results suggest that the CRE site and CREB play an important role in thrombin-induced IL-6 gene expression in VSMCs. Transactivation of EGF-R and activation of ERK and p38 MAPK are involved in this process. CREB may be a novel transcription factor that regulates thrombin-induced gene expression.
 ...
PMID:Thrombin induces interleukin-6 expression through the cAMP response element in vascular smooth muscle cells. 1170 62

The designation of atherosclerosis as a chronic inflammatory process represents an exciting and logical paradigm shift for cardiologists. Plasma concentrations of interleukin-6 (IL-6) and its hepatic by-product C-reactive protein (CRP) appear to reflect the intensity of occult plaque inflammation and by inference may determine vulnerability to rupture. Indeed, circulating IL-6 levels are elevated in patients with acute myocardial infarction (AMI), and also in patients with unstable, but not with stable angina. Coronary sinus IL-6 concentrations are also increased after percutaneous coronary intervention (PCI), and late restenosis correlates with an increase in IL-6 concentration after the procedure, indicating that IL-6 expression may be not only related to instability of atheromatous plaques, but also to the formation of restenotic lesions after PCI. These observations suggest the advantage of screening for circulating IL-6 concentration and the use of anti-inflammatory treatment for those thought be at high risk to reduce the risk of future AMI.
 ...
PMID:Interleukin-6 and acute coronary syndrome. 1171 26

Migration of vascular smooth muscle cells (VSMC) is a crucial event in the formation of vascular stenotic lesions. Tumor necrosis factor-alpha (TNF-alpha) is elaborated by VSMC in atherosclerosis and following angioplasty. We investigated the role of nuclear factor-kappaB (NF-kappaB) in human VSMC migration induced by TNF-alpha. Adenoviral expression of a mutant form of the inhibitor of NF-kappaB, IkappaB-alphaM, suppressed TNF-alpha-triggered degradation of cellular IkappaB-alpha, inhibited activation of NF-kappaB, and attenuated TNF-alpha-induced migration. Further, IkappaB-alphaM suppressed TNF-alpha-stimulated release of interleukin-6 and -8 (IL-6 and IL-8). Neutralization of IL-6 and IL-8 with appropriate antibodies reduced TNF-alpha-induced VSMC migration. Addition of recombinant IL-6 and IL-8 stimulated migration. Collectively, our data provide initial evidence that TNF-alpha-mediated VSMC migration requires NF-kappaB activation and is associated with induction of IL-6 and IL-8 which act in an autocrine manner.
 ...
PMID:NF-kappaB is required for TNF-alpha-directed smooth muscle cell migration. 1172 52

Inflammation contributes to atherosclerosis, but assessment in humans is largely restricted to measurement of markers in blood. We determined whether MRI properties of large arteries were associated with markers of inflammation in serum. Double inversion recovery, fast spin-echo images of the common carotid arteries and infrarenal aorta were obtained at 1.5 T both before and after gadolinium-DTPA (0.1 mmol/kg) in 52 subjects > or =40 years of age, 17 of whom had no risk factors for atherosclerosis and thus served as controls. Twenty-two study participants had increases in wall thickness (14), T2-weighted signal intensity (11), and/or contrast enhancement values (7) that were >2 standard deviations (SDs) from control group mean values. Ten subjects in this group had evidence of focal plaques in the carotids (5) and/or aorta (6). Compared with the remaining 30 subjects, these 22 had significantly higher levels of interleukin-6 (3.53 +/- 2.46 vs. 1.97 +/- 1.37 pg/mL, P = 0.004), C-reactive protein (0.56 +/- 0.98 vs. 0.30 +/- 0.52 mg/dL, P = 0.019), vascular cell adhesion molecule-1 (572 +/- 153 vs. 471 +/- 130 ng/mL, P = 0.012), and intercellular adhesion molecule-1 (244 +/- 80 vs. 202 +/- 45 ng/mL, P = 0.015), and nonsignificant differences in levels of E-selectin (46.1 +/- 18.9 vs. 42.3 +/- 11.3 ng/mL, P = 0.369). Thus, MRI characteristics of the aorta and carotid arteries were associated with elevated serum markers of inflammation, frequently in the absence of definite atheroma. MRI of large arteries may provide a new approach to investigate the contribution of inflammation to atherogenesis.
 ...
PMID:Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans. 1174 26

Persistent infections with Chlamydia pneumoniae have been implicated in the development of chronic diseases, such as atherosclerosis and asthma. Although azithromycin, clarithromycin, and levofloxacin are frequently used for the treatment of respiratory C. pneumoniae infections, little is known about the dose and duration of therapy needed to treat a putative chronic C. pneumoniae infection. In this study, we investigated the effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on the viability of C. pneumoniae and cytokine production in an in vitro model of continuous infection. We found that a 30-day treatment with azithromycin, clarithromycin, and levofloxacin at concentrations comparable to those achieved in the pulmonary epithelial lining fluid reduced but did not eliminate C. pneumoniae in continuously infected HEp-2 cells. All three antibiotics decreased levels of interleukin-6 (IL-6) and IL-8 in HEp-2 cells, but this effect appeared to be secondary to the antichlamydial activity, as the cytokine levels correlated with the concentrations of microorganisms. The levels of IL-1beta, IL-4, IL-10, tumor necrosis factor alpha, and gamma interferon were too low to assess the effect of antibiotics. These data suggest that the dosage and duration of antibiotic therapy currently being used may not be sufficient to eradicate a putative chronic C. pneumoniae infection.
 ...
PMID:Effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on Chlamydia pneumoniae in a continuous-infection Model. 1179 50

The cardiovascular mortality rate is unacceptably high in patients with end-stage renal disease (ESRD), which suggests an accelerated atherogenic process. The cause(s) of the accelerated atherogenesis in ESRD patients are not known, though recent studies suggest that persistent infection, such as Chlamydia pneumoniae, and proinflammatory cytokines may contribute. Forty-five ESRD patients (26 men) aged 51 +/- 2 years was studied at a time-point close to start of dialysis treatment and again after about 12 months of dialysis treatment. By using noninvasive B-mode ultrasonography, we evaluated changes in a surrogate marker of atherosclerosis, calculated intima media (cIM) area, in the common carotid artery. C-reactive protein (CRP), S-albumin, and interleukin-6 (IL-6) assessed the presence of an inflammatory reaction. We also measured C pneumoniae antibodies by microimmunofluorescence, nutritional status by subjective global assessment, lipid parameters, smoking habits, and the presence of comorbidity close to the start of dialysis. No significant changes in the prevalence of carotid plaques or the mean cIM area were observed during the first 12 months of dialysis. However, because some patients showed marked increases in the cIM area during only 12 months of dialysis we divided the patients into 2 groups: 23 nonprogressors ((delta)cIM area -2.7 +/- 0.4 mm2) and 22 progressors ((delta)cIM area 3.6 +/- 0.7 mm2). Sex, age, body mass index, comorbidity, blood lipid levels, S-albumin, and CRP levels did not differ significantly between the 2 groups. On the other hand, progressors had a significantly elevated basal median level of IL-6 (5.7 versus 3.1 pg/mL; P < 0.05) and an increased prevalence of positive (> or 1/64) immunoglobulin (Ig) A antichlamydia antibodies (59% versus 17%; P < 0.01) compared with nonprogressors. A significant positive (R = 0.41; P < 0.01) correlation was found between Log IL-6 and changes in the cIM area during 12 months of dialysis. In a stepwise multiple regression model, Log IL-6 did predict, independently (P < 0.01) of traditional risk factors and C pneumoniae antibodies, changes in the cIM area. These data suggest that a persistent chlamydial infection stimulates IL-6 levels, which in turn may be involved in the pathogenesis of accelerated carotid atherosclerosis in dialysis patients.
 ...
PMID:Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivity. 1184 Mar 67

Inflammatory cytokines play important roles in coronary artery disease. We investigated the clinical significance of monocyte-related cytokine expression in patients with angina pectoris. We studied 26 patients with stable effort angina and 20 patients with unstable angina in whom stenotic lesions of the coronary arteries were confirmed by selective coronary angiography. Plasma levels of interleukin-6 (IL-6), macrophage colony stimulating factor (MCSF), and monocyte chemoattractant protein-1 (MCP-1) were measured. Plasma levels of IL-6, MCSF, and MCP-1 in patients with unstable angina were significantly higher than those in patients with stable angina or control subjects. Patients with unstable angina were further divided into sub-groups according to their clinical classification; Levels of IL-6, MCSF, and MCP-1 in patients, who had anginal attacks at rest within the 48 h prior to admission (Braunwald class IIIB) were significantly higher than those in patients, who did not have attacks at rest (class IB). Five unstable patients, who were refractory to medical therapy and were referred for emergency coronary revascularization showed marked elevation of plasma MCSF and MCP-1 levels. In conclusion, plasma levels of monocyte-related cytokines were elevated in unstable angina. These increases were marked in patients with unstable angina with recent ischemic attack at rest, suggesting that activation of monocytes is involved in vulnerability of underlying atheromatous plaque.
Atherosclerosis 2002 Apr
PMID:Increased levels of monocyte-related cytokines in patients with unstable angina. 1188 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>