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)

Protein malnutrition, a condition associated with an albumin concentration less than 3.5 g/dL, has been shown to be a major risk factor for increased mortality in hemodialysis patients. The aim of this cross-over study was to evaluate the relationship between the type of membrane adopted and serum albumin changes by measuring peripheral blood mononuclear cells (PBMC) interleukin-6 (IL-6) release, serum albumin, and plasma concentrations of C-reactive protein (CRP) in 18 patients dialyzed with different membranes. During the study, all patients were dialyzed with cuprophan (CU), synthetically modified cellulosic (SMC) membrane (a new cellulosic membrane with lesser complement activation), and cellulose diacetate (CD) membrane, and have served as their own controls. IL-6 spontaneous release by PBMC resulted after 3 months of SMC (436.2 +/- 47.4 pg/mL) significantly (P < 0.05) reduced as compared with CU (569.3 +/- 24.5 pg/mL). This effect was more evident after 6 months of dialysis with SMC (220 +/- 35.3 pg/mL, P < 0.01 versus CU and versus 3 months of SMC). The passage to CD membrane was followed by a progressive new increase in the IL-6 PBMC release (332.3 +/- 30.7 after 3 months, and 351.2 +/- 35.8 pg/mL after 6 months, respectively) that, however, remained significantly (P < 0.05) lower than CU. The behavior of CRP plasma levels resembled that of IL-6 PBMC release (23.3 +/- 4.7 in CU, 11.0 +/- 2.1 after 3 months in SMC, and 7.9 +/- 1.5 after 6 months in SMC, respectively). IL-6 release values were positively correlated with circulating levels of CRP (r = 0.3264, P < 0.002). Serum albumin increased after 6 months of dialysis with SMC membranes (3.25 +/- 0.09 g/dL in CU and 3.64 +/- 0.07 g/dL in SMC, P < 0.05). When the patients were switched to CD, serum albumin showed a slight, though not statistically significant, decrease. Serum albumin concentrations negatively correlated with both IL-6 release values (r = -0.247, P < 0.05) and CRP plasma levels (r = -0.433, P < 0.001). In conclusion, our data clearly show that a significant relationship exists between biocompatibility of the membranes and serum albumin changes; serum albumin levels, in fact, are negatively correlated with the PBMC spontaneous IL-6 release values and CRP circulating levels.
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PMID:Changes of serum albumin and C-reactive protein are related to changes of interleukin-6 release by peripheral blood mononuclear cells in hemodialysis patients treated with different membranes. 1184 Mar 66

Atherosclerotic plaques were likened histologically to healing inflammatory lesions by Russell Ross, who proposed a "response to injury" hypothesis for their formation. More recently, intraplaque inflammation has been postulated to play a role in thinning of the fibrous cap, plaque rupture, and superadded thrombosis. Potential causes for vascular injury include mechanical stress, smoke exposure, hypercholesterolemia, hyperhomocysteinemia, and chronic infection (direct, or indirect). Blood levels of inflammatory markers (e.g., C-reactive protein [CRP]; serum amyloid A [SAA]; fibrinogen; plasma viscosity; erythrocyte sedimentation rate [ESR]; leukocyte count, low serum albumin) have been associated with vascular risk factors and with prevalent and incident atherothrombotic cardiovascular disease (CVD) (coronary heart disease, [CHD]; stroke; and peripheral arterial disease). More recently, cytokines (e.g., interleukin-6 [IL-6]) and soluble adhesion molecules (e.g., intercellular adhesion molecule-1, vascular cell adhesion molecule-1) have been associated with both risk factors and disease; and offer potential therapeutic targets for nonspecific "anti-inflammatory" treatment of arterial disease. Infections associated with arterial disease include specific infections (Chlamydia pneumoniae, Helicobacter pylori) and nonspecific infections (periodontal infections, respiratory tract infections). Recent meta-analyses have shown that associations of serum markers of C. pneumoniae and H. pylori with arterial disease, risk factors, or potential intermediary mechanisms for disease are weaker than was first suggested by early reports. Likewise, further studies and meta-analyses are required to evaluate the epidemiologic relationships of CVD to periodontal infection and disease and to chronic pulmonary infections and disease. The weaker the associations between chronic infections and CVD, the larger is the size of randomized controlled trials required to establish (or exclude) a preventive effect of infection treatment. While control of chronic infection in the mouth, stomach or lungs is appropriate for its local effects, proving its efficacy in prevention of CVD presents a continuing challenge to medical science.
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PMID:The relationship between infection, inflammation, and cardiovascular disease: an overview. 1188 52

Changes in hemoglobin (HGB) and serum albumin (SA) concentration associated with the onset of symptomatic erythema nodosum leprosum (ENL) were studied by comparing the values obtained on the day thalidomide or prednisone therapy commenced, with each patients' preceding values. In three groups of ENL patients mean HGB values fell with statistical significance: 1) in 38 patients who had been begun on thalidomide in the decade of the 1990s and who had been receiving dapsone for a minimum of 6 months, mean HGB values fell from 13.19 gm/dl to 12.27 gm/dl, or 7.0%, p = 6.0 x 10(-6); 2) in 8 patients who were in the active patient file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean HGB values feel from 13.40 gm/dl to 11.96 gm/dl, or 10.7%, p = 0.0015; and 3) in 8 patients not overlapping with the preceding groups, who were treated with rifampin and minocylcine or clarithromycin mean HGB values fell from 13.25 gm/dl to 12.48 gm/dl, or 5.8%, p = 0.0035. In two groups of ENL patients SA values also fell with statistical significance: 1) in 34 patients who were begun on thalidomide in the decade of the 1990s and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.14 gm/dl to 3.77 gm/dl, or 8.9%, p = 1.2 x 10(-5); and 2) in 10 patients from the active file not overlapping with the preceding group, and who had been on dapsone for a minimum of 6 months, mean SA values fell from 4.45 gm/dl to 4.06 gm/dl, or 8.8%, p = 0.039. A brisk fall in HGB values was often accompanied by a fall in SA concentration, and vice versa. Recovery from extreme falls in HGB and SA values was complete in 13 weeks. Recovery occurred in the presence of continued dapsone treatment. The falls could be rapid, occurring too soon to be the result of decreased erythropoiesis or hepatic SA synthesis. This study provides no direct evidence as to the mechanism responsible for the fall in these two parameters, but an interleukin-6 mediated hemodilution is an attractive hypothesis. The ENL-associated fall in HGB values was distinct from dapsone-induced hemolysis and the anemia of chronic disease. The ENL-associated anemia is not a good reason to discontinue dapsone therapy.
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PMID:Decreases in mean hemoglobin and serum albumin values in erythema nodosum leprosum and lepromatous leprosy. 1203 93

Proinflammatory cytokines have been demonstrated to play a crucial role in the pathogenesis and physiopathology of various chronic inflammatory conditions including Crohn's disease (CD). Among these cytokines, interleukin-6 (IL-6) must be especially important because increased serum concentrations of acute phase proteins, reduced level of serum albumin, and remarkable thrombocytosis are all well-explained by the increased level of IL-6. Moreover, IL-6 is capable of stimulating even IL-6 receptor (IL-6R) negative cells such as vascular endothelial cells when complexed to soluble form of IL-6R (sIL-6R), and serum level of IL-6 as well as sIL-6R has been demonstrated to increase during inflammation. To investigate the therapeutic potential of IL-6 signaling blockade for CD, anti-IL-6R monoclonal antibody (mAb) was introduced to various murine models of colitis. Anti-IL-6R mAb successfully prevented wasting disease and the development of macroscopic and histological lesions. It suppressed the accumulation of ICAM-1 positive and Mac-1 positive cells in the lamina propria (LP) and the expression of ICAM-1 and VCAM-1 by vascular endothelial cells. Expansion of colonic and splenic CD4(+) T cells was reduced as well as the colonic expression of tumor necrosis factor alpha (TNF-alpha), IL-1beta, and interferon gamma (IFN-gamma) mRNA without affecting the production of transforming growth factor beta (TGF-beta), IL-10, and IL-4 mRNA. The treatment also suppressed established colitis by inducing LP T cell apoptosis. These results strongly suggest that specific targeting of IL-6/sIL-6R pathway will be a promising new approach for the treatment of CD, and the clinical trial of humanized anti-IL-6R mAb is now under way.
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PMID:Anti-interleukin-6 therapy for Crohn's disease. 1257 Aug 22

It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha(1)-antichymotrypsin (ACT), alpha(1)-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
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PMID:Inflammatory markers in matched plasma and cerebrospinal fluid from patients with Alzheimer's disease. 1282 39

IL-6 acts on target cells via the ligand-binding protein interleukin-6 receptor (IL-6R) and the affinity-converting and signal-transducing glycoprotein 130 (gp130). Soluble interleukin-6 receptor (sIL-6R) has an agonistic role because the soluble complex (IL-6/sIL-6R) can activate cells that do not express IL-6R and an antagonistic role as it enhances the inhibitory activity of sgp130. Soluble forms of both receptors, sIL-6R and sgp130, regulate the action of IL-6. sIL-6R was measured by a sensitive enzyme-linked immunosorbent assay in paired sera and cerebrospinal fluid (CSF) from 46 patients with inflammatory neurological diseases (IND), 45 patients with relapsing-remitting multiple sclerosis (RR-MS), 13 patients with primary progressive multiple sclerosis (PP-MS), 17 patients with other non inflammatory neurological diseases (NIND) and 13 mentally healthy individuals--healthy controls (HC). Patients with RR-MS had CSF sIL-6R levels comparable to those from patients with IND, but higher than patients with NIND and HC. A positive correlation between the CSF/serum albumin (QAlb) and CSF sIL-6R levels was observed in IND but not in RR-MS patients indicating that CSF sIL-6R levels in IND patients could be influenced by serum sIL-6R and blood brain barrier (BBB) permeability properties. RR-MS patients had higher values of [CSF/serum sIL-6R:CSF/serum albumin] (sIL-6R index) than IND patients suggesting that in multiple sclerosis (MS), the increase in CSF sIL-6R could be due to intrathecal synthesis of sIL-6R. The finding of increased CSF sIL-6R concentrations (>979 pg/ml) with sIL-6R index (>4.66), in correlation with positive oligoclonal bands in RR-MS patients, suggests that values of sIL-6R index > 4.66 indicate intrathecal increase of sIL-6R and might be used as an indicator of neuroimmunoregulatory and inflammatory processes in the central nervous system (CNS).
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PMID:Soluble interleukin-6 receptor (sIL-6R) in cerebrospinal fluid of patients with inflammatory and non inflammatory neurological diseases. 1579 May 23

The aim of this study was to determine the effects of mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) on development of porcine parthenotes and nuclear transferred embryos, and on their expression of implantation-related genes. In the presence of bovine serum albumin, mGM-CSF did not increase the percentage of oocytes that developed to the blastocyst stage and at day 7 did not increase cell numbers of embryos. Addition of 2 ng/ml GM-CSF to protein-free culture medium significantly increased the compaction and blastocoel formation of 1- to 2-cell parthenotes developing in vitro. However, total cell numbers were not increased when they were cultured in the presence of GM-CSF. Semi-quantitative reverse transcriptase polymerase chain reaction revealed that mGM-CSF enhances mRNA expression of the leukemia inhibitory factor receptor, but does not influence interleukin-6 or sodium/glucose co-transporter protein gene expression in blastocyst stage parthenotes. These results suggest that mGM-CSF may enhance viability of porcine embryos developing in vitro in a defined culture medium.
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PMID:Mouse granulocyte-macrophage colony-stimulating factor enhances viability of porcine embryos in defined culture conditions. 1530 96

Endotoxemia following extended hepatectomy may be a cause of postoperative death. Multiple organ failure related to septemia is a common cause of early mortality after liver transplantation. Fibronectins (Fns) are involved in cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, and ischemic injury. Studies were performed to determine whether Fn influences the survival rate of rats subjected to endotoxin-induced liver injury after partial hepatectomy. Male Sprague-Dawley rats were intravenously administered lipopolysaccharide (LPS) 48 hours after 70% hepatectomy. Prior to LPS administration, plasma Fn or bovine serum albumin was given intravenously. The survival rate of the Fn-treated group was higher than that of the controls. Fn prevented increases in serum enzyme activity and total bilirubin related to liver injury. The levels of inflammatory cytokines including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 interferon-gamma were also significantly lower in the Fn-treated than the control group. Furthermore, the number of apoptotic cells and the degree of necrosis in the remnant liver were significantly decreased in the Fn-treated rats compared with controls. These results indicate that Fn prevents endotoxin-induced liver injury after partial hepatectomy, at least in part through inhibiting the production of inflammatory cytokines, and the necrosis apoptosis in the remaining liver.
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PMID:Fibronectin protects endotoxin-induced liver injury after partial hepatectomy in rats. 1551 19

Multiple-organ failure related to septicemia is a common cause of early mortality after liver transplantation. Endotoxemia following living donor hepatectomy may be a cause of postoperative death. Plasma fibronectin (Fn) exerts a broad range of biological effects on cellular adhesion, motility, differentiation, apoptosis, hemostasis, wound healing, reticuloendothelial system function, and ischemic injury. We studied the therapeutic effect of plasma Fn in mice after an intraperitoneal injection of lipopolysaccharide (LPS) and d-galactosamine (GalN). Female Balb/c mice received simultaneous intraperitoneal injection of LPS (50 microg/kg) and GalN (400 mg/kg). Thirty minutes prior to GalN/LPS administration, plasma Fn or bovine serum albumin was given intravenously. A single administration of plasma Fn (500 mg/kg) protected in dose-dependent fashion against lethal shock after GalN/LPS challenge. Plasma Fn significantly reduced the serum tumor necrosis factor-alpha, interferon-gamma, and interleukin-6 levels and significantly increased the serum interleukin-10 levels after GalN/LPS administration. Furthermore, plasma Fn significantly inhibited liver necrosis at 9 hours after GalN/LPS injection. The fraction of apoptotic-positive cells in these plasma Fn-treated mice was significantly lower than in the control group. These results support the protective treatment of endotoxin-induced liver injury by plasma Fn.
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PMID:Fibronectin suppresses apoptosis and protects mice from endotoxic shock. 1556 Dec 70

Hepatitis C (HCV) is not an uncommon feature in hemodialysis (HD) patients and may be a cause of systemic inflammation. Plasma cytokine interleukin-6 (IL-6) is mainly produced by circulating and peripheral cells and induces the hepatic synthesis of C-reactive protein (CRP), which is the main acute phase reactant. The aim of this study was to investigate the influence of HCV on two markers of systemic inflammation, serum CRP and IL-6, in HD patients. The study included 118 HD patients (47% males, age 47 +/- 13 years, 9% diabetics) who had been treated by standard HD for at least 6 months. The patients were divided into two groups depending on the presence (HCV+) or absence (HCV-) of serum antibodies against HCV. Serum albumin (S-Alb), plasma high sensitivity CRP (hsCRP), IL-6, and alanine aminotransferase (ALT) were measured and the values were compared with those for 22 healthy controls. Median hsCRP and IL-6 values and hsCRP/IL-6 ratio were: 3.5 vs 2.1 mg/l, P < 0.05; 4.3 vs 0.9 pg/ml, P < 0.0001, and 0.8 vs 2.7, P < 0.0001, for patients and controls, respectively. Age, gender, S-Alb, IL-6 and hsCRP did not differ between the HCV+ and HCV- patients. However, HCV+ patients had higher ALT (29 +/- 21 vs 21 +/- 25 IU/l) and had been on HD for a longer time (6.1 +/- 3.0 vs 4.0 +/- 2.0 years, P < 0.0001). Moreover, HCV+ patients had a significantly lower median hsCRP/IL-6 ratio (0.7 vs 0.9, P < 0.05) compared to the HCV- group. The lower hsCRP/IL-6 ratio in HCV+ patients than in HCV- patients suggests that hsCRP may be a less useful marker of inflammation in HCV+ patients and that a different cut-off value for hsCRP for this population of patients on HD may be required to define inflammation.
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PMID:Effect of hepatitis C serology on C-reactive protein in a cohort of Brazilian hemodialysis patients. 1591 61


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