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)

Currently, radical retropubic prostatectomy is the standard procedure for clinically localized prostate cancer. The surgical technique has been continuously refined for decades, resulting in reduced morbidity and improved functional and oncologic results. Since the late 90s, radical prostatectomy has been increasingly performed laparoscopically. A search of the available data has found that the articles published so far have proven the feasibility of the laparoscopic procedure but never confirmed its less invasiveness. In accordance with previous studies that have evaluated the invasiveness of various open and laparoscopic procedures, our clinic, which has routinely performed both techniques for several years, addressed the question whether laparoscopic prostatovesiculectomy indeed induces less severe surgical trauma. This prospective nonrandomized comparison study of the University Clinic of Urology at the Martin-Luther University at Halle-Wittenberg recruited a total of 64 patients, who underwent laparoscopic radical prostatectomy (n = 32) or open retropubic prostatectomy (n = 32) from January 2003 to April 2004. Both patient groups were comparable as to preoperative staging, PSA value and Gleason score. Besides perioperative parameters, such as surgical time, intra- and postoperative complications, blood loss and transfusion rate, need for analgetics and length of hospital stay, the comparison included oncologic data, such as Gleason score, pathologic stage and numbers of positive specimen margins. To get objectively reproducible data, the range of the systemic answers concerning the surgically induced tissue trauma was recorded as laboratory data. In all patients, pre-, intra-, and postsurgical markers of the acute-phase C-reactive protein, serum amyloid A (SAA), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured. The transfusion rate was 6 % for laparoscopic prostatectomies and 12 % for open prostatectomies. A rectal tear had to be intraoperatively repaired in one laparoscopically operated patient. The postoperative use of analgetics was comparable in both groups. The median hospital stay was 12.4 days for the laparoscopic and 11.2 days for the open surgical group. For T2 tumors, positive specimen margins were found in 6 cases (17 %) of the laparoscopic and in 4 cases (12 %) of the open surgical group. As to the indicators of any systemic reaction, no significant difference could be found during the entire clinical course between both surgical methods. In comparison with patients who underwent conventional open prostatectomy, patients with laparoscopically radical prostatectomy had identical to slightly higher serum levels of the acute-phase parameters, as evidence of an equal or a discretely manifested systemic response to the surgical trauma. The so far assumed less invasiveness of laparoscopic radical prostatectomy is not objectively supported by the data from this study. Thus, surgical trauma and its linked invasiveness must be considered equal for both methods, at least for the time being.
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PMID:[Minimal invasiveness of laparoscopic radical prostatectomy: reality or dream?]. 1536 29

Infections caused by Gram-negative bacteria constitute one of the major causes of septic shock, which results from the inability of the immune system to limit bacterial spread during the ongoing infection. In the last decade, it has been demonstrated that vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are two endogenous immunopeptides, which together with three G protein-coupled receptors (VPAC1, VPAC2, and PAC1) exert a significant, therapeutic effect attenuating the deleterious consequences of septic shock by balancing pro- and anti-inflammatory factors. We have recently shown PAC1 receptor involvement in vivo as an anti-inflammatory receptor, at least in part, by attenuating lipopolysaccharide-induced production of proinflammatory interleukin-6. The present study deepens in the protective role of PAC1 receptor in septic shock, elucidating its involvement in the modulation of neutrophil recruitment and in the expression of different molecular sensors such as intercellular adhesion molecule-1, vascular cell adhesion molecule-1, fibrinogen, serum amyloid A, and nitric oxide as important, systemic players of the development of septic shock. Our results, using a mice deficient in PAC1 and a PAC1 antagonist, show that VIP and PACAP as well as the PAC1 receptor are involved in neutrophil recruitment in different target organs, in adhesion molecules expression, and in coagulation-related molecule fibrinogen synthesis. Thus, this study provides some important insights with respect to the involvement of PAC1 into the complexities of sepsis and represents an advantage for the design of more specific drugs complementing standard intensive care therapy in severe sepsis, confirming VIP and PACAP as candidates for multitarget therapy of septic shock.
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PMID:Analysis of the role of the PAC1 receptor in neutrophil recruitment, acute-phase response, and nitric oxide production in septic shock. 1566 28

In this study, we evaluated the predictive values of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) for determining the clinical course in febrile neutropenic patients. Daily plasma analyses during the fever course were performed in 101 episodes with fever and chemotherapy-induced neutropenia (neutrophil count <0.5 x 10(9)/L). Procalcitonin (PCT) and IL-6 values were significantly higher in febrile episodes in patients who developed complications. Procalcitonin with a cut-off value of < or =0.4 ng/mL or IL-6 < or =50 pg/mL 3 d after fever onset indicated daily high negative predictive values (NPVs) (91-100%) for episodes with complications. No marker could predict deterioration; however, daily low plasma concentrations of PCT or IL-6 during the first 8 d of fever were found to be a good predictor of no subsequent complications in neutropenic patients and therefore to be a helpful tool for limiting anti-microbial therapy.
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PMID:Assessment of systemic inflammation markers to differentiate a stable from a deteriorating clinical course in patients with febrile neutropenia. 1577 41

Chronic inflammation is common in hypertension and acts as an independent determinant of arterial blood pressure. Hypertensive patients are reported to have high circulating levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and C-reactive protein (CRP). Recently, angiotensin II receptor blockers (ARBs) have been shown to possess benefits in addition to their ability to lower blood pressure, including anti-inflammatory and antioxidative properties within the vasculature. We evaluated the effects of the angiotensin II receptor blocker, valsartan, on these inflammatory cytokines. Thirty-nine patients with essential hypertension participated. These subjects received valsartan, 40 to 80 mg/day. Serum TNF-alpha, IL-6, CRP, and serum amyloid A (SAA) were measured before and after 3 months of treatment with valsartan. Valsartan significantly decreased systolic and diastolic blood pressure (160 +/- 16/92 +/- 11 mm Hg to 147 +/- 21/84 +/- 11 mm Hg, P = 0.001/P = 0.001, respectively). Serum TNF-alpha (9.1 +/- 8.6 pg/mL to 6.1 +/- 1.0 pg/mL, P = 0.006) and IL-6 (9.3 +/- 1.7 pg/mL to 8.9 +/- 1.4 pg/mL, P = 0.005) were significantly reduced after treatment with valsartan. However, C-reactive protein and serum amyloid A did not change. The angiotensin II receptor blocker, valsartan, may inhibit the development of atherosclerosis by lowering serum pro-inflammatory cytokines.
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PMID:Effects of angiotensin II receptor blockade with valsartan on pro-inflammatory cytokines in patients with essential hypertension. 1630 95

We examined whether the 22beta-methoxyolean-12-ene-3beta,24(4beta)-diol (ME3738)-mediated selective induction of interleukin-6 increased alpha1-acid glycoprotein and serum amyloid A expression, and whether these proteins protected against liver injury in vitro and in vivo. ME3738 treatment in male mice increased gene expression of alpha1-acid glycoprotein subtypes and serum amyloid A 2 genes, and plasma concentration of serum amyloid A. Treatment with alpha1-acid glycoprotein at 5 mg/animal or serum amyloid A at 0.03 and 0.1 mg/animal prior to concanavalin A administration reduced multifocal necrosis in the liver. Treatment with alpha1-acid glycoprotein and serum amyloid A, but not alpha1-antitrypsin, protected Hep G2 cells against cell injury. These results suggest that alpha1-acid glycoprotein and serum amyloid A, increased by ME3738-induced interleukin-6, might protect against concanavalin A-induced liver injury.
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PMID:Protective effects of alpha1-acid glycoprotein and serum amyloid A on concanavalin A-induced liver failure via interleukin-6 induction by ME3738. 1676 39

The Finnish DPS (Diabetes Prevention Study) demonstrated that lifestyle intervention, aimed at increasing physical activity, improving diet, and decreasing body weight, reduced the incidence of type 2 diabetes in individuals with overweight and impaired glucose tolerance by 58%. Here, we studied which immunological markers at baseline predicted subsequent type 2 diabetes and whether there are immunologically defined subsets of subjects who are more or less responsive to the protective effects of lifestyle intervention. We randomly assigned 522 participants to a control group (n = 257) or a lifestyle intervention group (n = 265). Immunological parameters at baseline included high-sensitivity C-reactive protein (CRP), serum amyloid A, interleukin-6, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage migration inhibitory factor (MIF), and soluble intercellular adhesion molecule. In the control group, CRP was the best immunological predictor for progression to overt type 2 diabetes. In the intervention group, progression to type 2 diabetes was significantly higher in subjects with the highest RANTES concentrations and was lower in subjects with the highest MIF levels. Ratios of RANTES to MIF in the upper tertile were highly predictive of incident type 2 diabetes in the intervention group (P = 0.006), whereas the association was less pronounced in the control group (P = 0.088). Thus, systemic concentrations of immune mediators appear to be associated with the progression to type 2 diabetes and the prevention of type 2 diabetes by lifestyle changes.
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PMID:Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study. 1687 99

The orphan nuclear receptor liver receptor homolog 1 (LRH-1) has been reported to play an important role in bile acid biosynthesis and reverse cholesterol transport. Here, we show that LRH-1 is a key player in the control of the hepatic acute-phase response. Ectopic expression of LRH-1 with adenovirus resulted in strong inhibition of both interleukin-6 (IL-6)- and IL-1beta-stimulated haptoglobin, serum amyloid A, and fibrinogen beta gene expression in hepatocytes. Furthermore, induction of the hepatic inflammatory response was significantly exacerbated in HepG2 cells expressing short hairpin RNA targeting LRH-1 expression. Moreover, transient-transfection experiments and electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that LRH-1 regulates this cytokine-elicited inflammatory response by, at least in part, antagonizing the CCAAT/enhancer binding protein beta signaling pathway. Finally, we show, by using LRH-1 heterozygous mice, that LRH-1 is involved in the control of the inflammatory response at the hepatic level in vivo. Taken together, our results outline an unexpected role for LRH-1 in the modulation of the hepatic acute-phase response.
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PMID:Liver receptor homolog 1 is a negative regulator of the hepatic acute-phase response. 1694 22

We evaluated whether high circulating levels of serum amyloid A (SAA), fibrinogen, interleukin-6 (IL-6) or leukocytes count (LC), can provide any additional predictive value over that provided by hs C-reactive protein (hs-CRP) for the incidence of 5-year cardiovascular mortality, in 458 and 476 consecutive patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndromes (NSTE-ACS), respectively. By 5 years the incidence of cardiovascular mortality was 37.3% and 35.5% in patients with STEMI and NSTE-ACS, respectively. Each of the study inflammatory biomarkers conferred independent to clinical risk predictors (and to cardiac troponin I) long-term prognostic information (all p<0.05), but only LC provided additional predictive value over that provided by hs-CRP, in either cohort (p<0.05). By multivariate Cox regression analysis, hs-CRP (p<0.001 for both cohorts) and LC (p=0.009 and p<0.001 for STEMI and NSTE-ACS, respectively) were the only inflammatory biomarkers independently associated with the incidence of 5-year cardiovascular mortality. According to the present results high circulating levels of LC but not of SAA, fibrinogen or IL-6 can provide additional long-term predictive value over that provided by hs-CRP in patients with acute coronary syndromes.
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PMID:The impact of hs C-reactive protein and other inflammatory biomarkers on long-term cardiovascular mortality in patients with acute coronary syndromes. 1696 98

Metallothionein (MT) is a low-molecular-weight cysteine-rich protein which has a high affinity for metals. The synthesis of MT is induced by heavy metals such as cadmium and zinc. However, little is known about the induction of MT by tetravalent or pentavalent metals. We investigated the induction of MT synthesis by a pentavalent vanadium compound in mice. Hepatic MT concentrations were increased by subcutaneous injection of ammonium metavanadate (AMV) dose-dependently, and to the similar levels as those induced by zinc chloride. However, accumulation of vanadium in the liver was very low, while high concentrations of vanadium were detected in the kidney. High performance liquid chromatography/inductively coupled argon plasma-mass spectrometry (HPLC/ICP-MS) chromatogram of the liver cytosol of AMV-treated mice revealed that the major metal bound to MT was not vanadium, but zinc. The chromatogram of the liver cytosol of MT null mice demonstrated the existence of a low-molecular-weight vanadium-binding protein that is different from MT. A time-course study showed that concentrations of serum interleukin-6 (IL-6) and serum amyloid A (SAA), an acute-phase protein, increased after the AMV injection. To confirm the involvement of IL-6 in MT induction by AMV administration, IL-6 null and wild-type mice were injected with AMV. In IL-6 null mice, hepatic MT induction by AMV administration decreased significantly to about a half of wild-type mice. These data suggest that both IL-6-dependent and -independent mechanisms are involved in MT induction by vanadium compounds in mice.
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PMID:Pentavalent vanadium induces hepatic metallothionein through interleukin-6-dependent and -independent mechanisms. 1698 76

Metallothionein (MT) is a cysteine-rich protein that binds to and is inducible by heavy metals such as cadmium and zinc. However, the precise mechanism of MT induction by other metals remains unclear. In the present study, we investigated the mechanism of MT induction by manganese, focusing on the involvement of cytokine production. Administration of MnCl(2) to mice resulted in the induction of MT dose-dependently in the liver with little accumulation of manganese. Speciation analysis of metals in the liver cytosol showed that the major metal bound to the induced MT was zinc. Administration of MnCl(2) caused an increase in mRNA levels of interleukin-6 (IL-6) in the liver as well as an increase in serum levels of IL-6 but not those of other inflammatory cytokines. Subsequently, serum levels of serum amyloid A (SAA), an acute-phase protein induced by IL-6, increased with a peak at 24 h. However, no increase in serum alanine aminotransferase activity was observed, suggesting that manganese enhanced the production of IL-6 and SAA without causing liver injury. In response to IL-6, the expression of a zinc transporter, ZIP14, was enhanced in the liver, possibly contributing to the synthesis of hepatic zinc-MT. In IL-6-null mice, the induction of hepatic MT by treatment with MnCl(2) was completely suppressed to the control level. These results suggest that manganese is a unique metal that induces the synthesis of hepatic MT completely depending on the production of IL-6 without accompanying liver injury.
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PMID:Induction of metallothionein by manganese is completely dependent on interleukin-6 production. 1706 64


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