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)

A 71-year-old woman remained under the rubble of her house for 4 hours after an accidental gas explosion. She suffered from a crush syndrome associating fractures, minor skin burns (< 10% body surface area), inhalation lung injury and moderate hypothermia (34 degrees C). In addition to local signs of compression of the lower limbs, the patient presented with hypovolemic shock and developed acute renal failure on day 3. We describe here the variations in hemodynamic and oxymetric parameters and cytokine response during the first post-injury week. A vasoplegic state resulting from low systemic vascular resistances with progressively increasing cardiac index, oxygen delivery and oxygen consumption closely followed the brief hypovolemic shock. Tumor necrosis factor-alpha remained below normal levels while interleukin-6 increased markedly with a major peak on day 2, in parallel with the drop in systemic vascular resistances. Interleukin-6 is a mediator of impairment in cell membrane function and a vasoconstriction inhibitor. Isolated increased interleukin-6 has been previously reported in severely burned patients suggesting a pathophysiological and hemodynamic similarity between crush syndrome and burn injury.
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PMID:[Hemodynamic profile and serum cytokines in crush syndrome. Analogy with severe burns]. 868 94

The baboon response to intravenous infusion of Shiga toxin 1 (Stx-1) varied from acute renal failure, proteinuria, hyperkalemia, and melena with minimal perturbation of host inflammatory and hemostatic systems (high-dose group, 2.0 microg/kg; n = 5) to renal failure with hematuria, proteinuria, thrombocytopenia, schistocytosis, anemia, and melena (low-dose group, 0.05 to 0.2 microg/kg; n = 8). Both groups exhibited renal shutdown and died in 57 hours or less. Both groups produced urine that was positive for tumor necrosis factor and interleukin-6 although neither of these cytokines was detectable (</=5 ng/ml) in the general circulation. Light and electron microscopy showed organelle disintegration and necrosis of the renal proximal tubular epithelium and of the intestinal mucosal epithelium at the tips of the microvilli, both of which were previously shown to bear Gb3 receptors. The renal distal tubular epithelium was spared. The renal proximal tubular epithelial changes were accompanied by swelling of visceral epithelial cells (podocytes) and by swelling and detachment of endothelial cells of the glomerular capillaries. In addition, all of the animals receiving low-dose Stx-1 showed microvascular fibrin deposition and thrombosis in renal glomerular and peritubular capillaries in association with a fall in hematocrit and platelet count and a rise in schistocyte count. The gastrointestinal villous tip lesions were accompanied by varying degrees of mucosal and submucosal congestion, hemorrhage, or necrosis. Electron microscopic images of cerebral cortex and cerebellum showed diffuse unraveling of myelin sheaths with occasional disintegration of neuronal cell bodies. In contrast to the gastrointestinal mucosal and renal proximal tubular epithelium, the Gb3 receptor glycolipid of the renal glomerular and neuronal tissues as determined using toxin overlay thin-layer chromatography plates was below the limit of detection (<13 pM/g wet tissue). We conclude that, depending on the status of the host and amount of toxin infused, Stx-1 can produce a variety of responses ranging from damage to cells carrying the Gb3 receptor (renal proximal tubular epithelial cells and gastrointestinal mucosa) to damage to renal glomerular tissues with microvascular thrombosis as a result of the host's inflammatory response localized to the kidney. We conclude that this thrombotic coagulopathy arises from local changes in the kidney because the appearance of host inflammatory mediators was limited to the urine. This suggests that the initial host response is localized in the kidney, and that the systemic thrombocytopenia, anemia, and schistocytosis may arise secondarily.
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PMID:Characterization of the baboon responses to Shiga-like toxin: descriptive study of a new primate model of toxic responses to Stx-1. 1023 66

Eleven patients with massive effusion due to pleuritis carcinomatosa were treated by tube drainage, followed by instillation of OK-432 and minocycline for pleurodesis. Pleural immunological and chemical reactions of adhesion were strongly induced by the use of these adhesive agents. As a result, pleural effusion was diminished in all patients without recurrence, allowing the drainage tubes to be successfully removed. As severe adverse effects following this course of therapy, high fever was observed in all patients, and acute renal failure in one. Blood chemical data from the patients revealed an increase in the number of granulocytes with a high level of interleukin-6 one day after instillation. These findings suggested that the symptoms of general inflammation were induced by local pleural inflammation. The median survival period was 253.7 days for 5 patients who were sufficiently fit to be discharged from our hospital. This was better than the historical average for the patients with uncontrolled pleural effusion. In conclusion, it was possible to control malignant pleural effusion and achieve longer survival periods through the optimal management of tube drainage and instillation of adhesion-inducing agents.
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PMID:[Adhesion therapy for malignant pleural effusion (intrapleural administration of OK-432 with minocycline)]. 1048 58

Postdiarrheal hemolytic uremic syndrome is caused by Shiga toxin (Stx)-producing Escherichia coli. It was shown previously that the baboon, like the human, has glycolipid receptors for Stx in the gut and the kidney and that a single 50- to 200-ng/kg intravenous dose of purified Stx-1 results in thrombocytopenia, hemolytic anemia, and renal thrombotic microangiopathy. For further characterization of factors that modulate disease expression, the baboon's response to the intravenous administration of 100 ng/kg Stx-1 given either rapidly as a single bolus or slowly as four 25-ng/kg doses at 12-h intervals was compared. Animals that received the Stx-1 as a single dose developed thrombocytopenia, schistocytosis, and acute renal failure. Urinary but not plasma tumor necrosis factor-alpha concentrations rose significantly by 6 h and then declined rapidly. Urinary and plasma interleukin-6 concentrations rose later. Glomeruli showed reduced patency of capillary loops, fragmented red blood cells, fibrin and platelet microthrombi, necrosis and detachment of endothelial cells, and accumulation of flocculent material in subendothelial spaces. Damage to tubular epithelium and peritubular capillary endothelium also was seen. Animals that received four divided doses of Stx-1 developed no clinical or histologic features of hemolytic uremic syndrome. It is concluded that in the primate model, disease expression is modulated by the rate of Stx administration, and it is speculated that in the human, the rate of Stx absorption from the gut is one determinant of disease severity.
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PMID:Response to single and divided doses of Shiga toxin-1 in a primate model of hemolytic uremic syndrome. 1142 74

The term hemolytic uremic syndrome (HUS) was first introduced to describe a heterogeneous group of diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Substantial progress has been made in our understanding of the etiology and pathogenesis of HUS. This article reviews some of the classic and new concepts related to the pathogenesis of Shiga toxin (Stx)-HUS and discusses their clinical relevance for the diagnosis and treatment of this syndrome. Infection with Stx-producing bacteria can induce HUS after a prodromal illness with or without diarrhea. Stx-induced renal endothelial injury is the primary pathogenic event. However, Stx also damages mesangial cells, as well as glomerular and renal tubular epithelial cells. Young children are at greatest risk for Stx-HUS because they express high levels of Stx receptors in renal glomeruli. Older children and adults express lower levels of glomerular Stx receptors and may develop Stx-HUS whenever the combined effects of lipopolysaccharide and cytokines upregulate the expression of Stx receptors and sensitize glomerular endothelial cells to Stx-induced injury, activate the coagulation-fibrinolytic system, and induce endothelial injury. Chemokine receptors and cytokines released by inflammatory cells (i.e., monocyte chemoattractant protein-1, interleukin-6, interleukin-8,) or injured endothelial cells (i.e., basic fibrobast growth factor) may play roles in this process. Measurement of the activity of a von Willebrand factor protease in plasma may help distinguish patients with thrombotic thrombocytopenic purpura from those with Stx-HUS.
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PMID:Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome. 1237 20

The aim of this study was first, to evaluate the effects of continuous hemodiafiltration (CHDF) alone or combined with CHDF and polymyxin-B immobilized fiber (PMX) on survival rates of patients with sepsis and acute renal failure, and second, to evaluate the changes in plasma levels of inflammatory cytokines before and after treatment with CHDF and PMX and CHDF alone in these patients. Forty-eight patients with septic shock and acute renal failure were enrolled in this study. The survival rate of all patients at 28 days was 25% for those with CHDF and 75% for those with PMX and CHDF treatment. Combination treatment produced a significant reduction of plasma levels of endotoxin and interleukin-6 compared to the basal values and to the treatment with CHDF alone. From these data, it is suggested that the combined therapy with PMX and CHDF is effective in improvement of survival rate of patients with septic shock and acute renal failure.
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PMID:Continuous hemodiafiltration with polymyxin-B immobilized fiber is effective in patients with sepsis syndrome and acute renal failure. 1210 50

A 52-year-old Japanese man presented with fever spikes, generalized fatigue, anorexia, and anasarca. The patient was referred for the evaluation of fever of unknown origin in association with swelling of cervical, axillary, and inguinal lymph nodes. He also manifested nephrotic syndrome, acute renal failure, hepatosplenomegaly, massive pleural effusion, ascites, disseminated intravascular coagulation, and hypergammaglobulinemia. C-reactive protein was positive and plasma vascular endothelial cell-derived growth factor (VEGF) and serum interleukin-6 levels were markedly elevated. Lymph node biopsy results showed that findings were compatible with Castleman's disease of hyaline vascular type associated with interfollicular plasmacytosis. In conjunction with the clinical findings, a diagnosis of multicentric Castleman's disease was made. The patient underwent renal biopsy because of nephrotic syndrome, and the results showed proliferation of mesangial cells, lobulation of glomeruli, and tram track pattern of the capillary wall without immune complex deposition. Electron microscopy showed widening of the subendothelial space. No electron-dense deposits were present in both mesangial and subendothelial regions. Pathologic features were compatible with glomerular microangiopathy and membranoproliferative glomerulonephritis-like lesions. With corticosteroid therapy, systemic symptoms disappeared; both VEGF and interleukin-6 levels were normalized, and he went into complete remission of nephrotic syndrome. In this article, the role VEGF plays in the pathogenesis of nephrotic syndrome and glomerular microangiopathy is discussed.
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PMID:Multicentric Castleman's disease associated with glomerular microangiopathy and MPGN-like lesion: does vascular endothelial cell-derived growth factor play causative or protective roles in renal injury? 1471 66

Acute renal failure (ARF) affects about 10% of severely ill neonates. Recent studies have shown that genetic polymorphisms of proteins that play a role in neonatal physiology may contribute to individual susceptibility to both ARF and its risk factors. Our review summarizes the data collected to date. Studies have shown that the risk of preterm neonates for ARF is directly associated with a combination of high tumor necrosis factor-alpha producer and low interleukin-6 producer genotypes, as well as with low heat shock protein 72 producer genotype. Premature birth is itself the most important risk factor for a number of complications, including ARF, and recent studies have also shown an association between several maternal and fetal cytokine genetic polymorphisms and increased inflammatory response in preterm neonates. These polymorphisms could also be associated with increased risk for disorders such as sepsis and necrotizing enterocolitis, which lead to renal hypoperfusion and ARF. Genetic polymorphisms of the renin-angiotensin-aldosterone system have not been shown to directly influence risk for ARF. They may, however, be associated with patent ductus arteriosus, poor postnatal adaptation, and heart failure, which are all prevalent risk factors for ARF.
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PMID:Genetic polymorphisms and risk for acute renal failure in preterm neonates. 1562 70

T cells have been demonstrated to modulate ischemia-reperfusion injury (IRI) in kidney, lung, liver and intestine. The underlying mechanisms for T-cell engagement in IRI are unknown. We hypothesized that the T-cell receptor (TCR) plays a role in renal IRI, and examined the effects of TCR alpha/beta (alphabeta) and gamma/delta (gammadelta) deficiency on ischemic acute renal failure (ARF). TCR-specific deficiency in specific mice was confirmed by fluorescence-activated cell sorting analysis using monoclonal antibodies (Abs). IRI was induced by bilateral clamping of kidney pedicles for 30 min, followed by reperfusion. Serum creatinine and kidney histopathology were used to assess the severity of experimental ARF. TCR alphabeta-deficient mice were significantly protected from kidney dysfunction compared to wild-type (WT) littermates after IRI (P<0.05). Histologic analysis demonstrated a significant reduction in renal tubular injury in both TCR alphabeta- and gammadelta-deficient mice compared to WT mice postischemia. TCR alphabeta-deficient mice had reduced tumor necrosis factor-alpha and interleukin-6 protein expression in kidney tissue compared to WT mice at 24 h postischemia using a microbead-based protein detection platform. Relative protection from kidney IRI did not correlate with neutrophil and macrophage infiltration of kidney tissue. Thus, the TCR plays a direct but modest pathophysiological role in kidney IRI. These data suggest that alloantigen-independent activation in IRI can lead to engagement of antigen-specific molecules on T cells. Furthermore, given that the TCR is already a target for diagnostics and therapeutic strategies in immune diseases, these approaches can now be harnessed for IRI.
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PMID:Role of the T-cell receptor in kidney ischemia-reperfusion injury. 1645 57

We described a 33-year-old man with gross hematuria and acute renal failure, who had suffered from fever for 6 months, multiple cervical lymph node swelling, splenomegaly, left-sided pleural effusion. He also suffered from anemia, thrombocytopenia, hypergammaglobulinemia, and his serum interleukin-6 levels were markedly elevated. Antiglomerular basement membrane antibodies were positive in the patient's serum. Lymph node biopsy results were compatible with Castleman disease of "plasma cell" variant. Renal biopsy revealed cellular crescents in most of the glomeruli. Immunofluorescence studies showed strong deposition of IgG in a linear pattern along the glomerular basement membrane. Pathologic features were compatible with crescentic glomerulonephritis because of antiglomerular basement membrane disease. With intensive plasmapheresis and monthly chemotherapy (cyclophosphamide, oncovin, prednisone regimen), the patient experienced clinical and biochemical remission. Although autoimmune phenomenon had been described frequently in Castleman disease, to the best of our knowledge, this was the first report that the patient with rapid progressive glomerulonephritis mediated by antiglomerular basement membrane antibodies, which might be associated with Castleman disease.
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PMID:Antiglomerular basement membrane disease associated with Castleman disease. 1930 55


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