UNIPROT:P05231 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Plasma tumour necrosis factor (TNF) and interleukin-6 (IL-6) levels of 18 infants with necrotizing enterocolitis (NEC) were measured at the time of diagnosis or on transfer to a paediatric surgical unit. Whereas TNF levels were similar for infants managed medically (stage II, n = 8) and surgically (stage III, n = 7), IL-6 levels were significantly higher in stage III cases (mean, 3,127 pg/mL [95% CI, 1,809 to 4,445 pg/mL]) than in stage II (mean, 127 pg/mL [95% CI, 10 to 329 pg/mL]; P = .001). Neither TNF nor IL-6 level predicted eventual outcome. Plasma IL-6 may be useful as an indication for operation in NEC.
...
PMID:Plasma interleukin-6 and tumour necrosis factor levels as predictors of disease severity and outcome in necrotizing enterocolitis. 807 25

Plasma concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured by ELISA in samples taken from 24 infants with necrotizing enterocolitis (NEC) between 0 and 306 h from diagnosis. TNF was detected (> 10 pg/ml) in 71% samples with a mean of 48 pg/ml (95% CI 42 to 55 pg/ml) and did not vary with either time from diagnosis or severity of disease. IL-6 was raised during the first 48 h with a significant difference between stage II (mean 127 pg/ml, 95% CI 10 to 329 pg/ml) and stage III (mean 3127 pg/ml, 95% CI 1809 to 4445 pg/ml, p = 0.001). Postoperative plasma IL-6 concentration fell to similar levels seen in stage II (mean 150 pg/ml, 95% CI 37 to 283 pg/ml, p = 0.79). We conclude that plasma concentration of IL-6 rather than TNF reflects the clinical severity of necrotizing enterocolitis and that the relative level of these cytokines has important implications for the use of anti-cytokine therapy in NEC.
...
PMID:Plasma cytokine levels in necrotizing enterocolitis. 808 74

We hypothesized that plasma levels of cytokines such as interleukin-6 and tumor necrosis factor (TNF) are elevated in critically ill infants with sepsis and necrotizing enterocolitis (NEC) and that the magnitude of their elevation is correlated with mortality rate. We measured plasma levels of interleukin-6 and TNF in 62 newborn infants with suspected sepsis or NEC. Eighteen infants had bacterial sepsis, 9 had bacterial sepsis plus NEC, and 15 had NEC but negative culture results. Twenty comparably ill infants with negative results on culture of systemic specimens served as study control subjects. Interleukin-6 levels were five- to tenfold higher in infants with bacterial sepsis plus NEC at the onset of disease than in infants with bacterial sepsis alone, in infants with NEC but negative culture results, and in control infants (p < 0.01). These differences persisted throughout the 48-hour study period. Interleukin-6 levels were also significantly higher in nonsurvivors than in survivors (p < 0.001). In contrast, plasma TNF values were not consistently increased in any of the groups. We conclude that plasma interleukin-6 is a more reliable indicator of bacterial sepsis and NEC than plasma TNF and may identify infants who might benefit from immunotherapeutic strategies.
...
PMID:Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis. 807 69

Necrotizing enterocolitis (NEC) is a neonatal disorder of unknown cause characterized by rapid necrosis of the bowel, primarily the ileum and colon. It is a worldwide problem. NEC is the most common gastrointestinal emergency in the neonatal intensive care unit, and ranks second as a cause of neonatal death. The incidence of NEC is inversely proportional to the birth weight and the degree of maturity. Infants born at or before 28 weeks gestational age have not received 80 per cent of the magnesium and 67 per cent of the copper found at term. Congenital deficiencies of these essential minerals may be compounded by high renal or gastrointestinal losses and high metabolic demand during the preterm infant's accelerated growth. Platelet thrombi appear early in the intestinal microvasculature in NEC. Platelet thrombosis and release of vasoconstrictor, platelet aggregating thromboxane A2 (TXA2) in human NEC appears to potentiate the intestinal ischaemia and necrosis in neonates who develop NEC. Magnesium and copper deficiency each enhance the synthesis of TXA2. Plasma levels of the inflammatory cytokines tumour necrosis factor (TNF) and interleukin-6 (IL-6) are increased in NEC and in magnesium deficiency; these experimentally produce shock and tissue injury, especially of the intestine. The synthesis of the potent vasoconstrictor endothelin is increased in magnesium deficiency. NEC has been regarded as a luminal insult that causes local generation of destructive oxygen free radicals. Tissues from animals deficient in magnesium are more susceptible to oxidative injury and lipid peroxidation than tissues from normal animals. Magnesium and copper deficiency impair antioxidant defence through decreased synthesis of glutathione and reduced activity of Cu/Zn superoxide dismutase, respectively. Although the aetiology of NEC is unknown, there appears to be sufficient data to implicate magnesium and possibly copper deficiencies in the pathogenesis. Consequences of deficiency of one or both minerals may include increased synthesis or activity of injurious mediators: IL-1, IL-6, TNF, TXA2, endothelin, and oxygen free radicals. A prospective trial of magnesium supplementation, but not copper supplementation, in very premature neonates can be recommended, with NEC as one of the outcome measures.
...
PMID:A review of evidence for a role of magnesium and possibly copper deficiency in necrotizing enterocolitis. 881 95

Concordance between gram-negative enteric and other toxin-producing bacteria in blood and stool culture, endotoxin (lipopolysaccharide), and interleukin-6 (IL-6) was measured in 60 preterm infants (600-1600 g) as a clinical index in neonatal necrotizing enterocolitis (NEC). E. coli, Klebsiella, Enterobacter, and Clostridium spp., identified by routine bacteriology, were each strongly associated with elevated concentrations of endotoxin (P < 0.01) in stool filtrates, with Clostridium spp. most strongly associated with NEC disease. Stool filtrate endotoxin (EU/g) measured by a Limulus amebocyte lysate assay was age dependent. Samples from stage I NEC (61%) and infants with advanced disease (67%) had notably elevated levels of stool endotoxin (> 10 ln EU/g) compared to NEC-negative (47%) samples tested. Plasma and stool IL-6 generally tested at the low, nonmeasurable limit of the ELISA for NEC-negative (88%) and stage I NEC (93%), although a small proportion of samples (25%) from infants with stage II or III NEC had elevated stool concentrations of IL-6. We conclude that identification of toxin-producing organisms and endotoxin elevations in stool filtrates are more useful than circulating levels of endotoxin in plasma in predicting mucosally limited disease in the gastrointestinal tract. The prognostic value of monitoring stool endotoxin in infants with overgrowth of gram-negative bacteria has implications for therapeutic strategies in patients with early and advanced stages of disease. Monitoring inflammatory cytokines (IL-6) in relation to endotoxin values in stool appears of limited clinical value in controlling this devastating disease in preterm neonates.
...
PMID:Concordance of bacterial cultures with endotoxin and interleukin-6 in necrotizing enterocolitis. 905 20

The objective of this study is to determine if the detection of interleukin-6 (IL-6) in maternal plasma prior to delivery predicts neonatal and/or infectious complications in patients with preterm premature rupture of membranes. Patients with preterm premature rupture of membranes between 24 and 35 weeks' gestation were asked to participate in the study. Maternal blood was obtained prior to delivery. All patients received Ampicillin-sulbactam and steroids. IL-6 concentrations were determined by enzyme-linked immunoadsorbent assay (ELISA) using 50 mL of plasma assayed in duplicate. ELISA sensitivity was 18 pg/mL. Neonatal and infectious complications examined were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, intra-amniotic infection, presumed neonatal sepsis, neonatal sepsis, and congenital pneumonia. Fifty-seven patients' plasma was analyzed. Thirty-five had positive plasma IL-6 prior to delivery. Twenty-seven patients had at least one neonatal complication with 24 (89%) being positive for IL-6. Of the 30 patients without complications, only 11 (37%) were positive (p = 0.0001, OR 13.8. 95% CI, 2.93-74.7). A subanalysis of patients who received a course of corticosteroids was performed and significance was maintained. Ten of 13 patients (77%) with neonatal complications had positive IL-6 compared with 40% without complications (p <or=0.01). Infectious morbidity occurred in 32 patients with 24 having positive IL-6 values (75%). Only 11 of 25 (44%) without infections were positive (p <or=0.03, OR 3.82, 95%, CI 1.09-13.0). The presence of IL-6 in the maternal plasma predicted patients with neonatal complications. These correlations persisted when the data were stratified for those patients who received corticosteroids. It also predicted infectious complications.
...
PMID:Detection of interleukin-6 in maternal plasma predicts neonatal and infectious complications in preterm premature rupture of membranes. 1173 92

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.
...
PMID:Genetic polymorphisms and risk for acute renal failure in preterm neonates. 1562 70

Necrotizing enterocolitis (NEC) is an inflammatory intestinal disorder that affects 2%-5% of all premature infants. Enterobacter sakazakii, a common contaminant of milk-based powdered infant formula, has been implicated as a causative agent of sepsis, meningitis, and NEC in newborn infants, with high mortality rates. However, the role played by E. sakazakii in the pathogenesis of NEC is, to date, not known. Here, we demonstrate for the first time that E. sakazakii can induce clinical and histological NEC in newborn rats. E. sakazakii was found to bind to enterocytes in rat pups at the tips of villi and to intestinal epithelial cells (IEC-6) in culture, with no significant invasion. Exposure to E. sakazakii induced apoptosis and increased the production of interleukin-6 in IEC-6 cells and in the animal model. These data suggest that E. sakazakii could be a potential pathogen that induces NEC and triggers intestinal disease by modulating enterocyte intracellular signaling pathways.
...
PMID:Enterobacter sakazakii enhances epithelial cell injury by inducing apoptosis in a rat model of necrotizing enterocolitis. 1858 83

Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB <32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery.
...
PMID:Maternal serum interleukin-6, C-reactive protein, and matrix metalloproteinase-9 concentrations as risk factors for preterm birth <32 weeks and adverse neonatal outcomes. 2019 52

Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in preterm neonates are associated with significant mortality and morbidity, including long-term neurodevelopmental impairment and socioeconomic burden. Safe and effective drugs for the prevention and treatment of these conditions are urgently needed. Pentoxifylline, a synthetic theobromine derivative, is a non-steroidal immunomodulating agent with unique hemorrheologic effects which has been used in a range of infectious, vascular, and inflammatory conditions in adults and children. The unique properties of pentoxifylline explain its potential benefits in preterm neonates with sepsis, NEC, and CLD, conditions characterized by activation of the inflammatory cytokine cascade, free radical toxicity, and impaired microcirculation. Pentoxifylline has anti-inflammatory properties resulting from inhibition of erythrocyte phosphodiesterase. It lowers blood viscosity and improves microcirculation and tissue perfusion. As a phosphodiesterase inhibitor, pentoxifylline downregulates pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Methylxanthines, including caffeine, theophylline, and theobromine are relatively non-toxic drugs; of these, theobromine is the least toxic. Pentoxifylline-related significant adverse events are thus very rare. Unlike other methylxanthines, pentoxifylline does not have significant cardiac and bronchodilating effects at therapeutic doses. Although it is contraindicated in adults with recent cerebral hemorrhage due to its effect on platelets, red blood cells, and plasma fibrinogen levels, no significant adverse effects including thrombocytopenia and bleeding have been reported in critically ill preterm neonates with sepsis or NEC after treatment with pentoxifylline. Based on data from pilot randomized trials and observational studies, our systematic review suggests that pentoxifylline may reduce mortality and/or morbidity in preterm neonates with sepsis, NEC, and CLD. Results of experimental studies also indicate that pentoxifylline may potentially be beneficial in meconium aspiration syndrome and hypoxic ischemic encephalopathy. Given the substantial burden of sepsis, NEC, and CLD in high-risk preterm neonates, and the findings of this systematic review, pentoxifylline needs to be evaluated urgently as a preventative and therapeutic agent for these conditions in randomized controlled trials that can detect minimal clinically significant effect sizes. Further clinical and experimental studies are also necessary to evaluate whether pentoxifylline is safe and effective in meconium aspiration syndrome and hypoxic ischemic encephalopathy.
...
PMID:Pentoxifylline in preterm neonates: a systematic review. 2079 59

1 2 Next >>