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 brain is no longer considered immune-privileged due to its capability of producing cytokines in response to neurotrauma; however, the cellular sources of cytokines have not been defined. This study focused on the production of four inflammatory cytokines, interleukin-1 (IL-1alpha), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interferon gamma (IFN-gamma) in primary culture of astrocytes under two different injury models which simulated in vivo mechanical trauma (scratch injury) and ischemia. Results demonstrated that astrocytes after scratch injury were positively immunostained with IL-1alpha, IL-6, and TNFalpha. A slot-blot study of culture media showed that the release of IL-1alpha, IL-6, TNFalpha, and IFN-gamma by astrocytes subsequent to scratch and ischemic injury reached approximately twice the control values. The temporal expression of these cytokines was different for the two models. All four cytokines began to increase 1 h postscratch and remained at high levels throughout the experiment. In the ischemic model, however, the increase of cytokine expression was delayed until 4-8 h of ischemia, when sharp increases were seen in all four cytokines. In this culture system, the exogenous influence of blood-borne factors and leukocytes, which occur with in vivo trauma and ischemia, was eliminated. Accordingly, the cytokines detected in the culture media were derived from astrocytes. This study provides the first evidence that astrocytes, without the influence from other cell types, can produce and release cytokines following mechanical and ischemic injury.
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PMID:Astrocytes produce and release interleukin-1, interleukin-6, tumor necrosis factor alpha and interferon-gamma following traumatic and metabolic injury. 1128 54

Hepatic ischemia/reperfusion leads to an excessive release of proinflammatory cytokines, which promotes local and remote cell damage. The value of cytokine measurement in humans for predicting graft function after orthotopic liver transplantation (OLT) remains unclear. Therefore, in this study, tumor-necrosis-factor-alpha (TNF-alpha), interleukin-6 (IL-6), and endotoxin (ET) levels were determined in the blood taken from the hepatic veins of 31 patients who underwent OLT. Peak levels of TNF-alpha in hepatic venous blood were measured shortly after reperfusion and were significantly higher than concentrations in the systemic circulation. IL-6 concentrations, peaking 90 min after reperfusion, only correlated with postoperative pulmonary dysfunction. ET was detectable in 21 patients, but levels did not correlate with either IL-6 or TNF-alpha concentrations. Additionally, serum cytokine levels did not correlate with the duration of ischemia or with histological changes seen in liver biopsies. In general, our study suggests that local secretion of cytokines does not predict liver function in the early posttransplant phase.
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PMID:Local secretion of TNF-alpha from the liver does not correlate with endotoxin, IL-6, or organ function in the early phase after orthotopic liver transplantation. 1137 Jan 71

JAK-STAT is the major downstream signal pathway of interleukin-6 (IL-6) cytokine family and is regulated by Tyr705 phosphorylation of Stat3. The present study examined the extent and the localization of phosphorylated Stat3 protein in brain tissue after focal ischemia in rats. The localizations of unphosphorylated and phosphorylated Stat3 were immunohistochemically examined in rats after 0.5 to 168 h of reperfusion following 1.5 h of middle cerebral artery occlusion (MCAO), induced by the intraluminal suture method. Absolute phosphorylated Stat3 immunoreactive cell counts were made in the cerebral cortex (ischemic core, peri-ischemia region, and contralareral cortex) and lateral striatal regions on both the ischemic and the contralateral sides. Stat3 protein was localized diffusely in cortical and striatal neurons in the sham-operated animals. Although weak Stat3 staining was detected in damaged neurons in the ischemic region, activated microglia, astrocytes, and endothelial cells clearly expressed Stat3 in this region. On the other hand, the sham group showed no phosphorylated Stat3 immunoreactivity. Phosphorylated Stat3 immunoreactivity was first detected in neurons after 3.5 h of reperfusion in each cortical and striatal region. Thereafter, Stat3 phosphorylation was marked in neurons in the peri-infarct region, peaked at 24 h, and then gradually declined throughout the reperfusion period. Endothelial cells expressed phosphorylated Stat3 in the ischemic core at 48 h of reperfusion. To identify the cellular source of phosphorylated Stat3, lectin histochemical study and immunohistochemical study with anti-microtubule-associated proten-2 and anti-glial fibrillary acidic protein antibodies were carried out. Double-staining immunohistochemistry with these cellular makers revealed phosphorylated Stat3 to be present in neurons, but in neither astrocytes nor microglia/macrophages. These results were also confirmed be western blot analysis. The present results indicate that Stat3 activation occurs in neurons and endothelial cells only during post-ischemic reperfusion despite widespread expression of IL-6 cytokines.
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PMID:Phosphorylation of signal transducer and activator of transcription-3 (Stat3) after focal cerebral ischemia in rats. 1142 84

The response of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1ra), macrophage colony stimulating factor (MCSF), white blood cell (WBC), platelet (Plt), lactic acid (LAC) to cardiopulmnary bypass (CPB) were studied until 48 hours after aortic declamping in 11 patients who underwent elective CABG (n = 4), mitral valve plasty or replacement with modified maze procedure (n = 5), and both procedures (n = 2). The highest levels of the cytokines IL-6, IL-8, IL-10, and IL-1ra were observed after the removal of the cross clamp. These cytokines just after the aortic declamping are likely to be occurred not only by an interaction of the blood components with the artificial surfaces, but also by ischemia-reperfusion injury upon discontinuation of the aortic clamping. MCSF increased gradually in the late post-CPB phase and reached a peak at 48 hr after aortic declamping. MCSF may play an important role in regulating hematopoiesis on the postoperative days 1 and 2 in patients. In conclusion, the therapy based on the kinetics of these cytokines would be useful for patients undergoing CPB.
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PMID:[Serum cytokine levels response to cardiac surgery with cardiopulmonary bypass]. 1145 22

Although anatomical and biochemical properties of the rat entopeduncular nucleus (EPN) closely resemble those of the substantia nigra pars reticulata (SNr), the present study shows that, unlike in the SNr, focal cerebral ischemia does not cause trans-synaptic degeneration of EPN neurons, despite striatal infarction and a similar delayed glial activation in both nuclei. In this study, interleukin-6 (IL-6) expression was found within EPN neurons 3 and 7 days after striatal ischemia. Since it has been reported that neuroprotective properties seem to predominate IL-6 function and that distinct SNr regions which demonstrate low trans-synaptic neuronal degeneration show high IL-6 expression and vice versa, IL-6 expression within partially deafferentiated but surviving EPN neurons could represent an intrinsic neuroprotective mechanism.
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PMID:Interleukin-6 expression in exo-focal neurons after striatal cerebral ischemia. 1156 53

Cardiopulmonary bypass (CPB) is associated with an immunological injury that may cause pathophysiological alterations in the form of a systemic inflammatory response syndrome (SIRS) or a multiple organ dysfunction syndrome (MODS). Previous studies on this issue have reported different changes of immunological parameters during and after CPB, but there are no reports about the lipopolysaccharide-binding protein (LBP) in relationship to other markers of inflammation in patients with MODS following cardiovascular surgery. In the present study, we investigated the acute-phase response of patients with MODS of infectious and non-infectious origin following open-heart-surgery. Plasma levels of procalcitonin (PCT), c-reactive protein (CRP), interleukin-6 (IL-6), and LBP were measured in the first four postoperative days in 12 adult male patients with the signs of SIRS and two or more organ dysfunctions after myocardial revascularization (MODS-group), and 12 patients without organ insufficiencies (SIRS-group). There were no significant differences regarding age, weight, height, preoperative NYHA-classification, preoperative LVEDP, or the number of anastomosis. Patients with MODS had a significantly longer operation time, duration of ischemia, and duration of extracorporeal circulation. None of the patients in the SIRS group died, whereas in the MODS group, 4 patients died due to septic multiorgan failure. Plasma PCT and IL-6 concentrations were significantly elevated in all MODS patients. CRP and LBP showed no differences between the MODS and the SIRS group. Comparing the MODS patients with and without positive microbial findings, we found significantly elevated levels of PCT and LBP in those patients with documented infections. Our results indicate that LBP may be a new marker for the differentiation between a severe non-infectious SIRS and an ongoing bacterial sepsis in the early postoperative course following CPB, while a microbiological result is still missing.
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PMID:Lipopolysaccharide-binding protein (LBP) and markers of acute-phase response in patients with multiple organ dysfunction syndrome (MODS) following open heart surgery. 1160 36

Ischemic preconditioning (IP) and pretreatment with lipopolysaccharide (LPS) reduce myocardial infarct size, but the precise mechanisms remain unknown. Rats were divided into 3 groups: the Control (C) group was subjected to 30 min ischemia followed by 3 h reperfusion; the IP and LPS groups had the same ischemia-reperfusion (I-R) insult with either preconditioning stimuli or pretreatment with LPS, respectively. Infarct size was smaller in the IP (23.4+/-2.3% of risk zone size) and LPS groups (28.5+/-2.0% of risk zone size) than in the C group (52.3+/-3.4% of risk zone size). Nuclear factor kappa-B (NF-kappaB) binding activity increased at 30 min reperfusion and declined thereafter, then rose again at 3 h reperfusion in the C group. The values in the IP (362% of control) and LPS (324% of control) groups were higher before I-R, and then decreased from 30 min (46% and 64% of control, respectively) until 3 h reperfusion (22% and 36% of control, respectively). Nuclear staining of NF-kappaB after reperfusion was less in the IP and LPS groups than in the C group. Expressions of cytokine mRNAs (interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha) were detected 30 min after the onset of reperfusion and their levels remained high after 3 h of reperfusion. These expressions of cytokine mRNAs after I-R were substantially suppressed by IP and LPS, although IP and LPS alone induced modest expressions of these cytokine mRNAs. These data suggest that IP and LPS contribute to infarct size reduction via the downregulation of NF-kappaB and the attenuation of cytokine gene expression.
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PMID:Ischemic preconditioning and lipopolysaccharide attenuate nuclear factor-kappaB activation and gene expression of inflammatory cytokines in the ischemia-reperfused rat heart. 1171 52

Interleukin-6 (IL-6) has been identified as a marker of ischemia. However, its association with bowel obstruction has not been studied. Fifty-seven patients diagnosed with bowel obstruction were evaluated in a prospective blinded study and managed either medically (n = 29) or surgically (n = 28) per decision of attending surgeon. Serum IL-6 levels were obtained at the time of diagnosis and serially during hospitalization. Mean IL-6 levels at the time of diagnosis were significantly higher in patients who required operation compared with medically treated patients (63.9 vs 19.6 pg/mL respectively; P = 0.027). Levels returned to those seen in medically treated patients 3 days after operation. There was no difference in temperature, white blood cell count, or lactic acid levels. Five patients required resection for ischemic bowel. Patients with ischemic bowel had significantly higher initial mean IL-6 (146.6 vs 45.9 pg/mL; P = 0.034) and lactic acid (23.6 vs 11.8 mg/dL; P = 0.035) at time of diagnosis compared with surgically treated patients without bowel ischemia. No difference in white blood cell count was seen. IL-6 was a sensitive predictor of patients with bowel obstruction requiring operation and for presence of ischemic bowel. IL-6 screening may allow for earlier and more selective operation potentially decreasing morbidity and mortality.
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PMID:Intravenous interleukin-6 levels predict need for laparotomy in patients with bowel obstruction. 1176 18

The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients.
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PMID:Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients. 1180 50

Despite extensive research, the exact mechanisms of cyclosporine A (CsA)-induced hypertension and nephrotoxicity remain obscure. Several lines of evidence suggest an involvement of the renin-angiotensin system (RAS) in CsA toxicity, but the issue is still controversial in more ways than one. Some interesting data of the interaction of CsA and RAS have been presented by us and others during the last years. In rats, activation of RAS by CsA is a consistent finding while the results from clinical studies show controversial results. The mechanisms of activation of RAS may be multifactorial. CsA increases renin release directly from juxtaglomerular cells. However, RAS activation may at least partly account for glomerular ischemia by vasoconstriction. A totally different view about the interaction of CsA and RAS has recently been presented. CsA antagonised the harmful effects of RAS over-expression on renal damage in double transgenic rats harbouring human renin and angiotensinogen genes. The protection was due to anti-inflammatory properties of CsA by inhibition of interleukin-6 and inducible nitric oxide synthase (iNOS) expression. Other studies have confirmed the inhibitory effect of CsA on iNOS. Calcium antagonists have been proposed to be the antihypertensive drugs of choice in treatment of CsA-induced hypertension because of their favourable haemodynamic effects on the kidneys. However, because angiotensin II plays a major role in the development of CsA-induced structural renal damage, pharmacological inhibition of RAS in CsA-treatment may have some beneficial effects beyond blood pressure control.
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PMID:Interaction of cyclosporine A and the renin-angiotensin system; new perspectives. 1187 76


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