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)

Fifty-seven patients with decompensated cirrhosis were studied prospectively to assess the sensitivity and specificity of early clinical or biological signs of bacterial infection. Among them, 19 had proven infection on admission (7 spontaneous bacterial peritonitis, 5 bacteraemia, 3 urinary tract infections, 2 pneumonia, 1 dental abscess and 1 cholangitis). Fever, polymorphonuclear cell count, fibrinogen and C-reactive protein levels were found to be of little or no help in diagnosing bacterial infection on admission. Interleukin-6 plasma levels were, however, significantly different between infected (median: 1386 pg/ml, range: 237-20,000) and non-infected patients (median: 34 pg/ml, range: 0-4500, p < 0.00001). Levels above 200 pg/ml were always found in infected patients, giving a sensitivity of 100% and a specificity of 74%. C-reactive protein correlated weakly with interleukin-6 levels, indicating a defective acute-phase response in cirrhosis. Tumor necrosis factor alpha plasma levels were less sensitive (95%) and specific (68%) for the diagnosis of bacterial infection at a threshold of 50 pg/ml, but were more closely related to a poor patient outcome. In decompensated cirrhosis, interleukin-6 plasma levels on admission provided the most sensitive and specific tool for the diagnosis of bacterial infection.
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PMID:Interleukin-6: an early marker of bacterial infection in decompensated cirrhosis. 793 Apr 84

Cytokines are low-molecular-weight protein mediators that possess a wide spectrum of inflammatory, metabolic, and immunomodulatory properties. Cytokines have been shown to be produced by monocytes/macrophages, lymphocytes, fibroblasts, endothelial cells, and more recently, hepatocytes and biliary epithelium. The aim of this study was to define biliary levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) in various disease states. Fifty-four patients undergoing ERCP comprised the study group. IL-6 and TNF-alpha were measured in aspirated bile using an ELISA technique. Levels of both TNF-alpha and IL-6 were significantly higher in patients with cholangitis (P < 0.00001). Moreover, IL-6 was 100% specific for cholangitis since none of the patients without bacterial cholangitis-including patients with biliary obstruction secondary to cholangiocarcinoma or pancreatic carcinoma-had measurable IL-6 in their bile. Low levels of biliary TNF-alpha were detectable in five patients without cholangitis; the sensitivity and specificity of TNF-alpha for cholangitis were 100% and 82%, respectively. There was a strong statistical correlation between biliary IL-6 and TNF-alpha levels (r = 0.819, P < 0.0001). In contrast, the correlations between biliary cytokines and serum biochemical parameters were weak. These results suggest that IL-6 and TNF-alpha are sensitive markers for cholangitis and may differentiate it from other types of biliary tract disease.
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PMID:Biliary interleukin-6 and tumor necrosis factor-alpha in patients undergoing endoscopic retrograde cholangiopancreatography. 920 Oct 97

Hepcidin is downregulated during progressive cholestasis in biliary atresia, but the mechanism is unknown. To verify whether downregulation of hepcidin is specific to cholestasis irrespective of the patient's age, we first analyzed liver hepcidin mRNA and protein expression in adults with primary biliary cirrhosis (PBC) (n=4), non-cholestatic cirrhosis (n=19) and in controls (n=9). We evaluated the tyrosine phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) expressions in the liver sections. A rat model of cholestasis by ligation of the extrahepatic bile duct (BDL) was created, and lipopolysaccharide (LPS)-induced cholangitis in cholestatic rats 2 weeks after BDL was also established to study the modulation of hepcidin by interleukin-6 (IL-6) and STAT3 signaling pathway in these models, using real-time quantitative reverse transcription-PCR, immunohistochemistry, western blotting and enzyme-linked immunosorbent assay (ELISA). An in vitro study of the effect of bile acids on hepcidin expression was carried out to re-confirm the in vivo findings. There was significantly lower hepcidin mRNA and pSTAT3 protein expression in cholestatic cirrhosis compared with non-cholestatic cirrhosis in adults. BDL caused significant decrease in hepcidin and gp130 mRNA expression compared with sham-operated group and normal control. Furthermore, there was significantly lower pSTAT3 protein expression and nuclear translocation in the cholestatic liver from the patients and the BDL rats, which was comparable to lower liver hepcidin mRNA and plasma hepcidin expression. Furthermore, BDL for 2 weeks attenuated the upregulation of hepcidin expression induced by LPS. Hydrophobic bile acid glycochenodeoxycholate inhibited IL-6-induced pSTAT3 expression in primary hepatocytes and resulted in the downregulation of hepcidin mRNA expression. In conclusion, the study shows that cholestasis or its important component-hydrophobic bile acids-can downregulate hepcidin expression through inhibiting IL-6-induced STAT3 phosphorylation and pSTAT3 protein nuclear translocation.
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PMID:Cholestasis downregulate hepcidin expression through inhibiting IL-6-induced phosphorylation of signal transducer and activator of transcription 3 signaling. 1965 45

Cholangiocarcinoma (CC) is emerging as an important treatment indication for photodynamic therapy. CCs are generally unresectable locally invasive tumors that occlude the biliary tree leading to fatal cholangitis and liver failure. Biliary decompression via stenting offers symptomatic relief but does not control tumor growth. Founded on an initial case study followed by ever more sophisticated clinical research, including randomized trials, photodynamic therapy has garnered enough momentum to be considered as part of the standard of care for these patients. Further, preliminary clinical data show the potential for benefit of the use of PDT in a neoadjuvant and adjuvant fashion to the minority of patients currently considered resectable or of border line resectability. PDT also impacts interleukin-6 levels and may form the basis for a targeted therapy approach to this disease. We review the clinical rationale, current studies and potential future directions of PDT for patients with CC.
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PMID:Cholangiocarcinoma: an emerging indication for photodynamic therapy. 1968 8

The 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model leads to chronic cholestatic liver injury and therefore resembles human diseases such as sclerosing cholangitis and forms of metabolic liver diseases. The role of the interleukin-6/glycoprotein 130 (gp130) system in this context is still undefined. Therefore, conditional gp130 knockout and knockin mice were used to achieve hepatocyte-specific deletions of gp130 (gp130(Deltahepa)), gp130-dependent ras (gp130(DeltahepaRas)), and signal transducer and activator of transcription (STAT) (gp130(DeltahepaSTAT)) activation. These mice were treated with a DDC-containing diet and analyzed over time. Mice deficient in hepatic gp130 and STAT signaling showed increased and earlier mortality than wild-type and gp130(DeltahepaRas) animals. Over time, significantly more apoptosis and cholestasis became evident in gp130(Deltahepa) and gp130(DeltahepaSTAT) mice. These mice also displayed increased tumor necrosis factor-alpha expression, a diminished acute-phase response (lack of STAT3 and serum amyloid A activation), and enhanced immune cell infiltration in the liver. These were associated with stronger periportal oval cell activation. In addition, DDC treatment in gp130(Deltahepa) and gp130(DeltahepaSTAT) mice resulted in significantly stronger hepatic stellate cell activation. Long-term analysis revealed the development of severe liver fibrosis in gp130(Deltahepa) and gp130(DeltahepaSTAT) animals, as evidenced by increased collagen accumulation. Here we demonstrate that gp130/STAT signaling in hepatocytes provides protection in a cholestatic hepatitis mouse model. STAT3-dependent signaling pathways in hepatocytes protect from apoptosis and tissue injury, which subsequently reduce oval cell activation and prevent fibrosis progression.
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PMID:Lack of glycoprotein 130/signal transducer and activator of transcription 3-mediated signaling in hepatocytes enhances chronic liver injury and fibrosis progression in a model of sclerosing cholangitis. 2038 1

Cholangiopathies are a diverse group of progressive diseases whose primary cell targets are cholangiocytes. To identify shared pathogenesis and molecular connectivity among the three main human cholangiopathies (biliary atresia [BA], primary biliary cholangitis [PBC], and primary sclerosing cholangitis [PSC]), we built a comprehensive platform of published data on gene variants, gene expression, and functional studies and applied network-based analytics in the search for shared molecular circuits. Mining the data platform with largest connected component and interactome analyses, we validated previously reported associations and identified essential and hub genes. In addition to disease-specific modules, we found a substantial overlap of disease neighborhoods and uncovered a group of 34 core genes that are enriched for immune processes and abnormal intestine/hepatobiliary mouse phenotypes. Within this core, we identified a gene subcore containing signal transduction and activator of transcription 3, interleukin-6, tumor necrosis factor, and forkhead box P3 prominently placed in a regulatory connectome of genes related to cellular immunity and fibrosis. We also found substantial gene enrichment in the advanced glycation endproduct/receptor for advanced glycation endproducts (RAGE) pathway and showed that RAGE activation induced cholangiocyte proliferation. Conclusion: Human cholangiopathies share pathways enriched by immunity genes and a molecular connectome that links different pathogenic features of BA, PBC, and PSC. (Hepatology 2018;67:676-689).
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PMID:Gene-disease associations identify a connectome with shared molecular pathways in human cholangiopathies. 2886 56

BACKGROUND Hodgkin lymphoma (HL) is a potentially curable disease with favorable outcomes. However, elderly patients with HL usually have more adverse prognostic factors and hence a much worse prognosis than younger patients. CASE REPORT The patient was a woman in her 80s. She reported high fever, anorexia, and a weight loss of 8 kg within 5 months. She had been on treatment for diabetes mellitus and hypertension. She had undergone percutaneous coronary intervention and pacemaker implantation to treat acute coronary syndrome and sinus arrhythmia, respectively. Blood tests showed elevation of alkaline phosphatase, C-reactive protein, leukocyte count, CA 19-9, and carcinoembryonic antigen. Computed tomography did not show tumors in the liver, and cholangitis and sepsis were suspected. Aspartate transaminase, alanine aminotransferase, and total bilirubin gradually increased through the course of the patient's hospital stay. Despite treatment, her condition deteriorated and she died 22 days after hospital admission. At autopsy, we found stage IV HL with lymph node swelling on both sides of the diaphragm, as well as diffusely disseminated nodules in the liver and spleen. CONCLUSIONS Our patient had several poor prognostic factors including B symptoms, comorbidity, advanced stage, Epstein-Barr virus infection, and expression of programmed death-ligand 1 and interleukin-6, all of which were closely connected with her advanced age. Her age and comorbidities may have been the most adverse prognostic factors for her illness. An effective HL screening method for elderly individuals should be developed to ameliorate poor prognosis and adverse outcomes.
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PMID:An Autopsy Case of an Elderly Patient with Classic Hodgkin Lymphoma Presenting with a Plethora of Clinical Symptoms and Signs. 3308 92