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 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

Pro-inflammatory cytokines, in addition to their role in host defence, can be considered a disease mediator; therefore, a reduction in cytokine synthesis or its effects is becoming a target of many diseases. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that could play a role in several clinical problems related to dialysis treatment. Biological activities of IL-6 could be modulated by two soluble circulating receptors, namely sIL-6R and sgp130. sIL-6R can enhance the inflammatory effects of IL-6 and; therefore, is an "agonistically" acting molecule. On the contrary, sgp130 efficiently binds the IL-6/sIL-6R complex with "antagonistic" effects. In this study we evaluated sgp130 release by peripheral blood mononuclear cells (PBMC) harvested from 10 healthy controls (CON) and 11 end-stage renal disease (ESRD) patients undergoing renal dialysis therapy RDT) with cellulosic hemophan membrane (HD). We also evaluated gp130 gene expression by reverse transcriptase polymerase chain reaction (RT-PCR). gp130 is the membrane bound receptor of IL-6 that could be proteolytically cleaved to generate soluble sgp130. Our results demonstrated that HD. at basal conditions, showed a higher release of sgp130 as compared with CON. We also demonstrated by RT-PCR at basal conditions a higher gene expression of gp130 in HD, as compared with CON. These results took place in the absence of any mitogenic stimulation and suggest that in HD patients an inflammatory subclinical status increases sgp130 release. The results obtained after lipopolysaccharide (LPS) stimulation confirm the role of inflammation on the increased release of sgp130 in HD patients.
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PMID:[The IL-6 soluble receptors in hemodialyzed patients]. 1574 93

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

The pathogenesis of ischemic coronary events involves degradation of the extracellular matrix in atherosclerotic lesions. The cysteine protease inhibitor cystatin-C may be involved in this phenomenon. The association of plasma cystatin-C with the incidence of myocardial infarction-coronary death and angina, was examined in a nested case-control (two controls per case) design within the prospective cohort study (Prospective Epidemiological Study of Myocardial Infarction (PRIME Study)) which included 9,758 men aged 50-59 years who were free of coronary heart disease (CHD) on entry and followed for a 5-year period. Three hundred and thirteen participants suffered myocardial infarction or coronary death (n = 159) or angina pectoris (n = 154) during follow-up. Cystatin-C was positively correlated with body mass index (BMI), low-density lipoprotein (LDL)-cholesterol, triglycerides and several inflammatory markers such as fibrinogen (r = 0.18), C-reactive protein (CRP) (r = 0.24), interleukin-6 (= 0.20), tumor necrosis factor-alpha (TNFalpha) (r = 0.27) and two TNFalpha receptors: TNFR1A (r = 0.43) and TNFR1B (r = 0.41); and negatively with high-density lipoprotein (HDL)-cholesterol (r = -0.25). After adjustment for traditional risk factors (age, diabetes, smoking, hypertension, BMI, triglycerides, LDL- and HDL-cholesterol), cystatin-C was significantly associated with the occurrence of the first ischemic coronary event. However, this association was no longer significant when CRP was included in the analysis. A decrease in glomerular filtration rate did not explain higher cystatin-C in cases than in controls. Cystatin-C appears to participate in the inflammatory phenomenon observed in the atherosclerotic process. Cystatin-C is not a more predictive risk marker of CHD than CRP or interleukin-6, but could be useful in detecting moderate chronic renal disease.
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PMID:Plasma cystatin-C and development of coronary heart disease: The PRIME Study. 1604 22

Diabetic nephropathy is one of the major microvascular complications in diabetes and is the leading cause of end-stage renal disease worldwide. Among various factors, angiogenesis-associated factors such as vascular endothelial growth factor (VEGF)-A and angiopoietin (Ang)-2 are involved in the development of diabetic nephropathy. We previously reported the therapeutic efficacy of antiangiogenic tumstatin peptide in the early diabetic nephropathy model. Here, we examine the effect of endostatin peptide, a potent inhibitor of angiogenesis derived from type XVIII collagen, in preventing progression in the type 1 diabetic nephropathy mouse model. Endostatin peptide did not affect hyperglycemia induced by streptozotocin (STZ). Glomerular hypertrophy, hyperfiltration, and albuminuria were significantly suppressed by endostatin peptide (5 mg/kg) in STZ-induced diabetic mice. Glomerular mesangial matrix expansion, the increase of glomerular type IV collagen, endothelial area (CD31(+)), and F4/80(+) monocyte/macrophage accumulation were significantly inhibited by endostatin peptide. Increase in the renal expression of VEGF-A, flk-1, Ang-2, an antagonist of angiopoietin-1, transforming growth factor-beta1, interleukin-6, and monocyte chemoattractant protein-1 was inhibited by endostatin peptide in diabetic mice. Decrease of nephrin mRNA and protein in diabetic mice was suppressed by treatment with endostatin peptide. The level of endostatin in the renal cortex and sera was increased in diabetic mice. Endogenous renal levels of endostatin were decreased in endostatin peptide-treated groups in parallel with VEGF-A. Although serum levels of endostatin were decreased in the low-dose endostatin-peptide group, high-dose administration resulted in elevated serum levels of endostatin. These results demonstrate the potential use of antiangiogenic endostatin peptide as a novel therapeutic agent in diabetic nephropathy.
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PMID:Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model. 1618 90

Hypotension is an important complication of hemodialysis. The pathogenesis of this complication remains unclear. The role of chronic inflammation in chronic dialysis-associated hypotension has not been investigated. A total of 38 dialysis patients with chronic hypotension were identified. Their demographic and biochemical data, inflammatory markers (high sensitivity C-reactive protein [hs-CRP] and interleukin-6 [IL-6]), hepatocyte growth factor (HGF), leptin, and adiponectin levels were measured and compared with those of another 87 nonhypotensive dialysis patients. No between-group differences in their clinical features, underlying renal disease were found. Levels of serum albumin, leptin, adiponectin, and HGF were similar between the two groups. The serum albumin levels were inversely correlated with hs-CRP and IL-6. Adiponectin was negatively correlated with hs-CRP and leptin. HGF showed a positive relation with hs-CRP. No association was found between adiponectin and HGF. Therefore, chronic inflammation is prevalent in the dialysis population, and serum HGF level is associated with inflammation but not with chronic dialysis hypotension.
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PMID:Inflammatory markers and hepatocyte growth factor in sustained hemodialysis hypotension. 1630 55

Numerous prospective studies support the concept of postprandial glycaemia (PPG) as a risk factor for cardiovascular diseases (CVDs) in individuals with impaired glucose tolerance (IGT). A meta-analysis has demonstrated an exponential relationship between 2-hour postchallenge glucose levels and the incidence of CVD. This relationship is stronger than those observed with fasting glycaemia or glycosylated haemoglobin (HbA(1c)), and persists after adjustment for other vascular risk factors. Although there are fewer data available for the diabetic population, those that are available also support PPG as a risk factor for CVD. Treating PPG with acarbose is associated with a reduction in cardiovascular events in both patients with IGT and diabetes mellitus. Acarbose also reduces the progression of intima-media thickness (IMT), which is a surrogate endpoint for atherosclerosis. It has been suggested that the beneficial effect could be related to an improvement in postprandial hyperglycaemia and associated atherogenic factors - oxidative stress, endothelial dysfunction and pro-coagulation factors - and to an improvement in other cardiovascular risk factors such as systolic blood pressure (by decreasing water and salt absorption), postprandial hypertriglyceridaemia and insulin resistance. Treating PPG with glinides improves IMT as well as interleukin-6 and C-reactive protein levels, while treating PPG with rapid-acting insulin analogues is also associated with improvements in endothelial dysfunction. The Kumamoto study suggests that reduced PPG is strongly associated with reductions in retinopathy and nephropathy. Finally, decreasing PPG in patients with IGT reduces the progression of diabetes. In conclusion, physicians should increase efforts to control PPG in order to further improve HbA(1c), and should also ensure close control of postprandial hyperglycaemic peaks so as to optimise patients' chances of avoiding cardiovascular complications. As for the prevention of CVD, further prospective intervention trials, powered to answer this question, are still required.
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PMID:Should postprandial hyperglycaemia in prediabetic and type 2 diabetic patients be treated? 1652 17

Even apparently healthy patients on dialysis have significant loss of lean body mass. Patients with chronic renal failure without coexisting metabolic acidosis or inflammation have decreased protein turnover, with balanced reduction in protein synthesis and breakdown. However, regional and whole-body protein kinetic studies indicate that hemodialysis (HD) induces net increase in protein breakdown. Whole-body protein turnover studies show that HD is associated with decreased protein synthesis, but proteolysis is not increased. Muscle protein kinetics studies, however, identify enhanced muscle protein breakdown with inadequate compensatory increases in synthesis as the cause of the catabolism. Transmembrane amino acid-transport kinetics studies show that the outward transport is increased more than the inward transport of amino acids during HD. Altered intracellular amino acid transport kinetics and protein turnover during HD could be caused by the loss of amino acids in the dialysate or cytokine activation. Cytokines may be released from peripheral blood mononuclear cells and skeletal muscle during HD. Preliminary evidence indicates that intradialytic increase in cytokines activates the ubiquitin-proteasome pathway. An intradialytic increase in albumin and fibrinogen synthesis is facilitated by interleukin-6 and the constant supply of amino acids derived from skeletal muscle catabolism. Protein anabolism can be induced in end-stage renal disease patients by repletion of amino acids, and perhaps treatment with recombinant human insulin-like growth factor.
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PMID:Amino Acid and protein kinetics in renal failure: an integrated approach. 1653 Jun 7

The mortality rate among patients with chronic kidney disease is much higher than among those without. As glomerular filtration rate declines and patients approach end-stage renal disease, the mortality rate increases and patients at this stage are more likely to die than receive renal replacement therapy. The higher mortality and its underlying causes among chronic kidney disease patients is a serious issue. Lack of physician awareness of chronic kidney disease and its association with excess mortality remains a problem. In this review of current literature, we aim to increase this awareness among health care professionals and the general public and to call for action to improve survival in chronic kidney disease patients. The data strongly suggest that advancing kidney dysfunction leads to increased mortality risk. Contributing to the mortality associated with chronic kidney disease are the comorbidities that accompany this disease state. For instance, patients with chronic kidney disease and comorbidities are at 1.3 to 3.6 times more risk than patients without chronic kidney disease. Further, cardiovascular disease is the leading cause of death among chronic kidney disease patients. It appears that both traditional (such as diabetes mellitus, hypertension, and smoking) and nontraditional risk factors (C-reactive protein and interleukin-6 levels) present in the chronic kidney disease population promote the frequent development of cardiovascular disease. Therefore, therapies targeting both progression of chronic kidney disease and comorbidities such as cardiovascular disease are required to reduce mortality among these patients.
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PMID:Increased mortality in chronic kidney disease: a call to action. 1653 76

Using changes in cell counts and levels of cancer antigen 125 (CA125), fibrinogen degradation product (FDP), and interleukin-6 (IL-6) in effluent before and after the use of icodextrin-based peritoneal dialysis solution (icodextrin), we evaluated the effects of icodextrin on peritoneal membrane. The subjects were 8 anuric patients (4 men, 4 women) who had been using a 2.5% glucose-based dialysis solution (glucose solution) for the overnight dwell. The mean age of the patients was 57.9 +/- 6.1 years, and their mean duration of continuous ambulatory peritoneal dialysis was 61.6 +/- 44.3 months. In all patients, chronic glomerulonephritis was the cause of end-stage renal disease. We changed the 2.5% glucose solution used for the 8-hour dwell to an icodextrin, and we compared cell counts in effluent and levels of IL-6, FDP, and CA125 in the overnight effluent before, and 12 and 36 weeks after, the switch to the icodextrin. When 2.5% glucose solution was used for the overnight 8-hour dwell, the mean cell count in the effluent was 5.5 +/- 3 cells/mm3. However, 12 and 36 weeks after the start of icodextrin, mean cell counts in effluent were significantly increased to 15.3 +/- 7.7 cells/mm3 (p < 0.01) and 16.5 +/- 11.2 cells/mm3 (p < 0.01) respectively. Values of effluent CA125, FDP, and IL-6 obtained during the use of a glucose solution were compared to values obtained 12 and 36 weeks after the start of icodextrin. Effluent levels of CA125 and IL-6 did not vary before and after the use of the icodextrin, but levels of FDP in the icodextrin effluent were higher than the levels found in the effluent of a 2.5% glucose solution (7278.8 +/- 2915 ng/mL before the start of icodextrin; 29,875 +/- 13,227 ng/mL 12 weeks after icodextrin introduction, p < 0.01; and 12,062.9 +/- 5684.6 ng/mL 36 weeks after icodextrin introduction). Icodextrin induced a subclinical inflammatory response in the peritoneum. Therefore, biocompatibility of an icodextrin solution is not always superior to that of a glucose solution, and further research is needed to clarify the influence of long-term icodextrin use on the peritoneum.
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PMID:Effect of icodextrin-based peritoneal dialysis solution on peritoneal membrane. 1668 79


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