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)

The evolution and the relationship between inflammatory and renal-injury markers in women with acute uncomplicated pyelonephritis under antimicrobial therapy were investigated in a prospective study. Markers were measured before and 6 and 24 h after the intravenous administration of 1 g of ceftriaxone. Before treatment, the median levels of all markers except the serum creatinine levels were high. Twenty-four hours after the onset of antibiotic treatment, the C-reactive protein (CRP) level continued to be high, while the serum interleukin-6 (IL-6) levels and the urine IL-6, IL-8, albumin, and immunoglobulin G (IgG) levels decreased significantly. In contrast, serum creatinine and tumor necrosis factor alpha levels and urine N-acetyl-beta-glucosaminidase, alpha1-microglobulin, and beta2-microglobulin levels did not change over time. There was a significant correlation between IL-6 and IL-8 levels and urine albumin and IgG levels (urine albumin and IgG levels are glomerular and urinary tract-injury markers) as well as between serum CRP levels and the levels of the tubular-injury markers. In women with acute pyelonephritis, appropriate antibiotic treatment rapidly decreases serum IL-6 levels and urine IL-6 and IL-8 levels, which correlate well with urine albumin and IgG levels.
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PMID:Evaluation of inflammatory and renal-injury markers in women treated with antibiotics for acute pyelonephritis caused by Escherichia coli. 1471 61

Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity factor in sepsis and organ injury, in part by initiating the release of inflammatory mediators. We wanted to elucidate the structural requirements of PepG to trigger inflammatory responses and organ injury. Injection of native PepG into anesthetized rats caused moderate but significant increases in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and urea (markers of renal dysfunction) in serum, whereas PepG pretreated with muramidase to digest the glycan backbone failed to do this. In an ex vivo model of human blood, PepG containing different amino acids induced similar levels of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10, whereas muramidase digestion nearly abolished the ability to induce cytokine release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG. However, additional experiments showed that muramidase-treated PepG synergized with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood, despite its lack of inflammatory activity when administered alone. Based on these studies, we hypothesize that the structural integrity of the glycan chain of the PepG molecule is very important for the pathogenic effects of PepG. The amino acid composition of PepG, however, does not seem to be essential for the inflammatory properties of the molecule.
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PMID:Organ injury and cytokine release caused by peptidoglycan are dependent on the structural integrity of the glycan chain. 1497 33

In the Cardiovascular Health Study, the authors sought to evaluate the impact of chronic renal insufficiency (CRI) on cardiovascular risk status and outcomes in a representative sample of community-dwelling elderly adults. Defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men, CRI was present in 647 (11%) of 5808 participants. At baseline, the prevalence of clinical or subclinical cardiovascular disease was 64% in participants with CRI and 43% in those without CRI (odds ratio, 2.34; 95% confidence interval, 1.96-2.80). The incidence of cardiovascular disease events during follow-up was 3% per year in participants with creatinine levels <1.10 mg/dL and increased steadily to reach 7% per year in those with creatinine > or =1.70 mg/dL. Among the possible mediators for the association between CRI and cardiovascular morbidity are inflammatory (C-reactive protein, fibrinogen, and interleukin-6) and hemostatic (factor VII, factor VIII, plasmin-antiplasmin product, and D-dimer) biomarkers, all of which were significantly elevated in Cardiovascular Health Study participants with CRI. Future studies should evaluate the contribution of novel and traditional cardiovascular risk factors to the cardiovascular risk of elderly persons with CRI. The identification of CRI in the elderly and the use of cardiovascular prevention therapies represent a major opportunity to reduce their burden of cardiovascular morbidity.
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PMID:Chronic renal insufficiency and cardiovascular events in the elderly: findings from the Cardiovascular Health Study. 1501 Jun 54

Peritoneal hyperpermeability has been associated with increased levels of effluent vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). Mesothelial cells can produce various vasoactive substances besides VEGF. A large mesothelial mass may possibly lead to high dialysate VEGF concentrations and may partly explain some cases of peritoneal hyperpermeability during a patient's early months on peritoneal dialysis (PD). Early peritoneal fast transport may therefore not necessarily be associated with systemic inflammation. To investigate the relationship of effluent markers and peritoneal transport, we measured the appearance rates of cancer antigen 125 (CA125), VEGF, and IL-6 in 4-hour effluents from 69 peritoneal equilibration tests (PETs) using 3.86% glucose solution. At the same time, we measured serum VEGF and IL-6. Our analyses included an early group (EG), whose members had been on PD for 4.6 +/- 3.3 months, and a later group (LG), whose members had been on PD for 30 +/- 17 months. In EG, dialysate-to-plasma creatinine at 4 hours (D/P(Cr240)) correlated significantly with effluent CA125/min (r = 0.51, p = 0.006) and VEGF/min (r = 0.57, p = 0.001), but not with serum VEGF or IL-6. The values of CA125/min and VEGF/min also correlated (r = 0.40, p = 0.034). Fast transporters in EG had higher effluent CA125 (p = 0.057) and VEGF (p = 0.0001), but not serum or effluent IL-6. In LG, D/P(Cr240) again correlated significantly with dialysate VEGF (r = 0.51, p = 0.009), but not with CA125. Fast transporters in LG tended to have higher levels of serum and effluent IL-6 and effluent VEGF. We conclude that fast solute transport rates at the beginning of PD are associated with signs of a large mesothelial cell mass and not consistently associated with higher systemic IL-6. The VEGF produced by mesothelial cells can mediate early peritoneal hyperpermeability in some populations. Later, mesothelial mass is lost and is no longer related to increased intraperitoneal VEGF or IL-6.
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PMID:Evaluation of effluent markers cancer antigen 125, vascular endothelial growth factor, and interleukin-6: relationship with peritoneal transport. 1538 86

We assessed the influence of the prophylactic use of a combination of the IV beta-adrenergic blocker, esmolol, and the phosphodiesterase III inhibitor, enoximone, on postbypass hemodynamic status, inflammation, and endothelial and organ function in a prospective, randomized, placebo-controlled study in 42 patients aged >65 yr undergoing aortocoronary bypass grafting. In 21 patients, esmolol (aim: heart rate <70 bpm) plus enoximone (initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and continued until the morning of the first postoperative day; another 21 patients received saline solution as placebo. Hemodynamics, splanchnic perfusion (gastric-arterial CO(2) gap), liver function (glutathione transferase-alpha plasma levels), renal function (creatinine clearance, urine concentrations of N-acetyl-beta-D-glucosaminidase), myocardial ischemia (creatine-kinase MB and troponin T plasma levels), inflammation (elastase, interleukin-6 and -8 plasma levels), and endothelial integrity (adhesion molecules plasma levels) were assessed at baseline, before and after cardiopulmonary bypass (CPB), and in the intensive care unit until the first postoperative day. Catecholamine requirements were significantly less in the treated than in the nontreated patients. Heart rate was significantly slower, cardiac index was higher, and gastric-arterial CO(2) gap was significantly lower in the treatment group. Troponin T, beta-N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and soluble adhesion molecules increased significantly in the untreated control, but remained almost normal in the esmolol+enoximone patients. Inflammatory responses (elastase/interleukins) were attenuated by esmolol+enoximone. We conclude that, in comparison to an untreated control, the prophylactic use of a combination of esmolol and enoximone in elderly patients undergoing cardiac surgery with cardiopulmonary bypass resulted in overall beneficial effects on postbypass hemodynamic status, organ function, inflammatory response, and endothelial integrity.
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PMID:The prophylactic use of the beta-blocker esmolol in combination with phosphodiesterase III inhibitor enoximone in elderly cardiac surgery patients. 2145 Oct 80

The aim of this study was to define the predictive values of serum and cerebrospinal fluid concentrations of interleukin-6 and neuron-specific enolase and urinary uric acid/creatinine ratio for outcome in term infants with perinatal asphyxia. All biochemical markers were measured simultaneously within the 24-72 hours of life in 21 infants. The infants were monitored with a standardized neurologic and developmental evaluation protocol over the 2 years of life. The overall outcome at 2 years of age was categorized as "favorable" or "adverse". According to Sarnat and Sarnat classification, 12 infants had mild encephalopathy and 9 infants had moderate to severe encephalopathy. Seven of 9 (78%) infants with moderate to severe encephalopathy had adverse outcome. However, all infants with mild encephalopathy had favorable outcome. Interleukin-6 and neuron specific enolase levels in cerebrospinal fluid and serum interleukin-6 levels were significantly correlated with the degree of encephalopathy, as well as the outcome. Interleukin-6 in cerebrospinal fluid (cutoff value, 25.9 pg/mL) had the highest predictive value among the biochemical markers. The predictive factors identified in this study should be examined for their ability in a fresh clinical sample in the neonatal intensive care unit before these markers can be applied to the routine clinical of infants with perinatal asphyxia.
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PMID:Value of biochemical markers for outcome in term infants with asphyxia. 1551 13

The therapeutic effect of M-2000 (C6H10O7) molecule was tested in Adriamycin-induced nephropathy. To induce experimental nephrosis, Adriamycin was given once by a single intravenous injection (7.5 mg/kg) through the tail vein. Six days after injection of Adriamycin, therapeutic protocol was developed by intraperitoneally (i.p) administration of 30 mg/kg M-2000 solution. Total of i.p. injections were 14, in which five injections were made every day and nine injections were carried out at regular 48-h intervals. Therapeutic protocol was terminated on day 28 and animals were killed on day 43. The treated patient rats showed a significant reduction in proteinuria, BUN, serum creatinine and serum cholesterol, as well as, administration of M-2000 could significantly diminish the serum level of interleukin-6 (IL-6) in treated animals compared to non-treated controls. Moreover, treatment with M-2000 significantly reduced number of glomerular leukocytes, Hypercellularity and hydropic change in capillary network within the renal cortex and decreased tubular casts. These data suggest that M-2000 therapy can ameliorate proteinuria, and suppress the progression of glomerular lesions in experimental model of nephrosis.
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PMID:M-2000, as a new anti-inflammatory molecule in treatment of experimental nephrosis. 1565 9

Ischemia-reperfusion (I/R) injury is associated with activation of coagulation and inflammation. Interestingly, various anticoagulants have been shown to reduce both coagulation and inflammation in animal models of kidney I/R injury. Fondaparinux is a synthetic pentasaccharide that selectively inhibits factor Xa (FXa) in the coagulation cascade. The aim of this study was to investigate the effect of fondaparinux in a lethal murine model of kidney I/R injury. A murine model of kidney I/R was established. In this model, we measured activation of the coagulation cascade and induction of inflammation. Administration of fondaparinux to I/R-injured mice reduced fibrin deposition in the kidney, reduced serum creatinine levels and increased survival from 0 to 44% compared with saline-treated control mice. Fondaparinux also reduced interleukin-6 and macrophage inflammatory protein-2 expression and decreased neutrophil accumulation in the injured kidneys. Finally, we showed that fondaparinux reduced thioglycollate-induced recruitment of neutrophils into the peritoneum and inhibited the binding of U937 cells to P-selectin in vitro. Our data suggest that fondaparinux reduces kidney I/R injury primarily by inhibiting the recruitment of neutrophils.
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PMID:The synthetic pentasaccharide fondaparinux reduces coagulation, inflammation and neutrophil accumulation in kidney ischemia-reperfusion injury. 1574 44

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease. Because serum markers of inflammation and the metabolic syndrome are also associated with atherosclerotic disease and insulin resistance, we investigated whether plasma homocysteine (Hcy) levels were associated with serum markers of inflammation and factors of metabolic syndrome in 223 elderly patients with type 2 diabetes mellitus. The levels of plasma Hcy and serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and C-peptide were measured. The C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The number of abnormal metabolic factors (presence of diabetes, blood pressure > or =130/85 mm Hg, triglycerides > or =150 mg/dL, high-density lipoprotein cholesterol <35 mg/dL (men) or <39 mg/dL (women), or body mass index >25 kg/m 2 ) was assessed. Elevated plasma Hcy levels correlated significantly with serum IL-6 ( r = 0.25, P < .001), C-peptide ( r = 0.22, P < .01), and the number of abnormal metabolic factors ( r = 0.20, P < .01), but not with C-reactive protein. Multiple linear regression analysis revealed that log-transformed IL-6, serum C-peptide, vitamin B12 , and creatinine were significant determinants of plasma Hcy levels. The correlation between Hcy and IL-6 levels was strongest in those with TT genotype of C677T MTHFR among 3 genotypes. The association between plasma Hcy and serum IL-6 levels supports the hypothesis that the activation of innate immunity is involved in the pathogenesis of arteriosclerosis in patients with diabetes mellitus who are homozygous for the TT genotype of C677T MTHFR.
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PMID:Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes. 1593 19

Chronic allograft nephropathy is characterized by chronic inflammation and fibrosis. Because retinoids exhibit anti-proliferative, anti-inflammatory, and anti-fibrotic functions, the effects of low and high doses of 13-cis-retinoic acid (13cRA) were studied in a chronic Fisher344-->Lewis transplantation model. In 13cRA animals, independent of dose (2 or 20 mg/kg body weight/day) and start (0 or 14 days after transplantation) of 13cRA administration, serum creatinine was significantly lower and chronic rejection damage was dramatically reduced, including subendothelial fibrosis of preglomerular vessels and chronic tubulointerstitial damage. The number of infiltrating mononuclear cells and their proliferative activity were significantly diminished. The mRNA expression of chemokines (MCP-1/CCL2, MIP-1alpha/CCL3, IP-10/CXCL10, RANTES/CCL5) and proteins associated with fibrosis (plasminogen activator inhibitor-1, transforming growth factor-beta1, and collagens I and III) were strikingly lower in treated allografts. In vitro, activated peritoneal macrophages of 13cRA-treated rats showed a pronounced decrease in protein secretion of inflammatory cytokines (eg, tumor necrosis factor-alpha, interleukin-6). The suppression of the proinflammatory chemokine RANTES/CCL5 x 13cRA in fibroblasts could be mapped to a promoter module comprising IRF-1 and nuclear factor-kappaB binding elements, but direct binding of retinoid receptors to promoter elements could be excluded. In summary, 13cRA acted as a potent immunosuppressive and anti-fibrotic agent able to prevent and inhibit progression of chronic allograft nephropathy.
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PMID:13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy. 1597 72


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