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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocytes play a significant role in vascular diseases. The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators. Pentoxifylline (PTX) has a well-demonstrated ability to act on the activated neutrophils. It increases chemotaxis and decreases their adherence to endothelial cells, oxidative burst, and enzyme release. In this preliminary study, we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils (PMN) activation and cytokine release. A double-blind, randomized, placebo-controlled trial was carried out in 14 patients (age range 46-86 years) suffering from critical ischemia, as defined by the European Consensus Document, or subacute ischemia due to occlusive arterial disease of the lower limb. Femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before (TO) and after infusion (T24) of PTX or placebo. PMN activation was evaluated by study of cell migration, beta 2 integrin expression (CD11b/ CD18), oxidative burst, and elastase release. Inflammation proteins were analyzed, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen. Before treatment, our results demonstrate an important activation in both femoral and antecubital venous blood. PMN activation markers, cytokine release, and other inflammation proteins were significantly increased compared with normal subjects. In the experimental group there was no significant difference between femoral and antecubital venous blood. Six patients received PTX infusion and seven patients were in the placebo group. The effect of PTX was evaluated after 24 h of treatment (1,200 mg). In the PTX group the following variables were improved compared with the placebo group: CD11b expression on PMNs, elastase released from PMNs, fibrinogen, CRP, TNF-alpha, and IL6 in plasma. These preliminary results should be interpreted with caution because of the small sample size. Further trials may contribute to more complete understanding.
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PMID:Leukocyte activation study during occlusive arterial disease of the lower limb: effect of pentoxifylline infusion. 869 73

The effects of transient global ischemia using bilateral carotid artery occlusion on regional cytokine levels in gerbil brain were investigated using enzyme-linked immunoassay techniques. Brain concentrations of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were increased during the early recirculation period ( < 6 h) after 10 min of ischemia, with lesser degrees of elevation following only 5 min of ischemia. TNF-alpha levels in the hippocampus and striatum were significantly increased as early as 1 h after recirculation, declining sharply to control levels by 12 h, then transiently increasing at 24 h. Elevated levels of IL-1 beta and IL-6 were not seen until 3-6 h post-occlusion. No significant increases in cytokine concentrations were observed in the cerebellum or thalamus. These results suggest that regionally selective increases in cytokines may be involved in the pathophysiological changes in hippocampus and striatum following transient cerebral ischemia.
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PMID:Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain. 871 Jan 73

Restoration of blood flow to an acutely ischemic lower limb may paradoxically result in systemic complications and unexpected mortality. It has been suggested that lower limb ischemia reperfusion alters gut permeability. In this study, using a rat model, we determined the effect of acute lower limb ischemia-reperfusion on mortality rate, bowel morphology, and circulating concentrations of endotoxin and the proinflammatory cytokine interleukin-6. Survival rate was compared in two groups of adult Wistar rats: (1) control group (n = 10); and (2) animals subjected to 3 hours of bilateral hind limb ischemia followed by reperfusion (n = 10). Both groups were observed under standard conditions for 4 days. In a second experiment three groups of animals were studied: (I) control (n = 12); (II) 3 hours of bilateral hind limb ischemia alone (n = 12); and (III) 3 hours of bilateral hind limb ischemia followed by 2 hours of reperfusion (n = 12). Animals subjected to bilateral hind limb ischemia followed by reperfusion had a significantly higher mortality rate (70%) than controls (0%) (p < 0.005). Morphometric assessment of the small bowel showed a significant decrease in mean mucosal thickness in the ischemia-reperfusion group compared with that in the group of controls and the ischemia-alone group (p < 0.05). Bilateral hind limb ischemia followed by reperfusion was associated with significantly increased plasma concentrations of endotoxin (p < 0. 05) and interleukin-6 (p < 0.0001) compared with that of controls and ischemia alone. These results indicate that reperfusion of the acutely ischemic lower limb is accompanied by structural changes in the gut mucosa associated with increased systemic endotoxin concentrations and cytokine activation. Mortality following reperfusion of the acutely ischemic limb may be related to a systemic inflammatory response triggered by endotoxin of gut origin.
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PMID:Mortality following lower limb ischemia-reperfusion: a systemic inflammatory response? 879 48

The hepatic response to injury is orchestrated by the expression of different gene groups (i.e., heat shock and acute phase). In the present study, the expression of heat shock and acute phase genes was analyzed in the context of a localized injury, regional hepatic ischemia-reperfusion. Left and median liver lobes were subjected to 1 h of ischemia, whereas blood flow was maintained to the remainder of the organ. After the period of ischemia, the organ was reperfused, and samples of the ischemic and nonischemic liver were obtained at different time points during reperfusion. Expression of the heat shock gene, HSP 72, was detected only in the ischemic liver, whereas expression of the acute phase gene, beta-fibrinogen, and the interleukin-6-inducible gene, metallothionein, was maximally induced in the nonischemic liver and attenuated in the ischemic liver. To determine how the heat shock and acute phase responses were reprioritized during stress, expression of beta-fibronogen and HSP 72 was induced simultaneously in the same animal by administration of endotoxin and total body hyperthermia, respectively. Administration of endotoxin did not impede the expression of HSP 72; however, heat shock attenuated, but did not eliminate, the endotoxin-induced expression of beta-fibronogen. These observations suggest that the heat shock and acute phase responses are not mutually exclusive.
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PMID:Distinct expression of heat shock and acute phase genes during regional hepatic ischemia-reperfusion. 885 85

Tumor necrosis factor (TNF) gene expression in rat retina following transient ischemia was studied by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Gene expression for other cytokines was also studied by RT-PCR. Although very little expression for TNF gene was detected in normal retina, it was markedly increased 0.5-48 h after reperfusion, with peak expression at 12 h (20-fold of control). Gene expression for interleukin-6, interferon-gamma, and transforming growth factor-beta 1 was also increased. The results provide evidence that retinal ischemia can up-regulate cytokine gene expression in the retina.
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PMID:Increased cytokine gene expression in rat retina following transient ischemia. 887 88

Interleukin-6 (IL-6) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro. However, it remains to be determined whether or not IL-6 rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused IL-6 continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. IL-6 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with IL-6 than in those receiving vehicle infusion. These findings suggest that IL-6 has a trophic effect on ischemic hippocampal neurons.
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PMID:Interleukin-6 prevents ischemia-induced learning disability and neuronal and synaptic loss in gerbils. 892 90

The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into tow independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.
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PMID:Hypoxia-induced modulation of endothelial cell properties: regulation of barrier function and expression of interleukin-6. 902 16

Gut-origin sepsis is a serious medical complication of military injuries following hemorrhage. Splanchnic ischemia induces intestinal necrosis leading to systemic bacteremia. Rat and mouse models of hemorrhagic shock were used to investigate bacterial translocation from the gut. Orally administered ameliorative treatments using the cytokine interleukin-6 (IL-6) were able to reduce or eliminate sepsis following hemorrhage. To mimic battlefield wounds and hemorrhage, anesthetized mice were bled from the femoral artery, held at a mean arterial blood pressure of 35 mm Hg for 1 hour, and then resuscitated with shed blood and 2-fold volume lactated Ringer's solution. Anesthetized rats were bled from the carotid artery at a rate of 15 ml/kg at 1 ml/minute. Bacteriological cultures of livers and mesenteric lymph nodes from hemorrhaged animals given recombinant IL-6 had significantly fewer colonies per gram of tissue than saline-fed controls. 125I-labeled IL-6 remained in the gut for up to 6 hours giving regional protection, whereas labeled interleukin-2 was disseminated throughout the body in the same time. In vivo and vitro studies of IL-6 showed that long incubations with high doses of trypsin, chymotrypsin, or intestinal contents were necessary to inactivate the bioactivity of this cytokine. Electron microscopy showed that epithelial cells from hemorrhaged mice fed saline had sparse or missing villi and vacuolated cytoplasm. Epithelial cells from control mice or mice hemorrhaged and fed cytokine appeared completely normal. Oral administration of IL-6 on the battlefield may be an important treatment for the prevention of sepsis following hemorrhage.
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PMID:Systemic sepsis following hemorrhagic shock: alleviation with oral interleukin-6. 915 11

The intestine plays a major role in the pathophysiology of multiorgan failure. Although the systemic inflammatory response might be induced by endotoxin released through bacterial translocation, other factors such as intestinal ischemia might be implicated. We investigated the relationship between intestinal ischemia-reperfusion and cytokine release in rat models of hemorrhagic or endotoxic shock. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and IL-6 mRNA expression, were assessed at the end of shock and resuscitation. Hemodynamic changes and lactate levels suggested the presence of intestinal ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increased by hemorrhage and further increased after saline resuscitation. Similar results were obtained with mRNA cytokine gene expression in macrophages. Endotoxin was not detectable in the hemorrhagic group. Endotoxic shock also increased production of cytokines, which, in contrast to hemorrhage, was not further increased by resuscitation. These results suggest that intestinal ischemia-reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine gene expression in the absence of endotoxin.
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PMID:Gut ischemia and mesenteric synthesis of inflammatory cytokines after hemorrhagic or endotoxic shock. 927 9

Interleukin-6 (IL-6) is an acute reactant cytokine with anti-inflammatory properties, which has been found to prevent injury in a model of acute hepatitis in mice through downregulation of tumor necrosis factor alpha (TNF-alpha); to correlate inversely with markers of hepatocellular injury in patients with liver ischemia; and to initiate liver regeneration in mice. In this study, we investigated the role of IL-6 in rodent models of hepatic warm ischemia/reperfusion (WI/Rp) injury. IL-6-deficient mice (-/-) were subjected to hepatic WI and compared with C57BL/6 mice, as well as IL-6 -/- mice pretreated with recombinant IL-6 (rIL-6). The effects of rIL-6 following various periods of ischemia were further studied in models of hepatic ischemia in rats. IL-6 -/- mice had increased reperfusion injury as assessed by transaminase levels and a tissue necrosis scoring system when compared with controls, an effect prevented by pretreatment with rIL-6. Similarly, rats pretreated with rIL-6 had reduced reperfusion injury and better survival than controls in each respective WI group. Tissue TNF-alpha expression measured by Northern blot analysis and serum C-reactive protein (CRP) levels, a marker of inflammation, were significantly reduced in animals pretreated with rIL-6. Administration of antibodies to TNF-alpha reproduced the beneficial effect of rIL-6. Hepatocyte proliferation, as assessed by a scoring method for mitotic index and proliferating nuclear cell antigen staining, was markedly increased in rIL-6-treated rats when compared with controls. In conclusion, this study suggests that IL-6 could play an important role in limiting hepatic warm ischemia/reperfusion (WI/Rp) injury, probably through its anti-inflammatory properties, modulation of TNF-alpha, and/or promotion of liver regeneration. rIL-6 might become an important cytokine in clinical situations associated with WI/Rp injury.
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PMID:Interleukin-6 protects liver against warm ischemia/reperfusion injury and promotes hepatocyte proliferation in the rodent. 939 92


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