Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-acetylcysteine (NAC) is an antioxidant and cytoprotective agent with scavenging action against reactive oxygen species and inhibitory effects on pro-inflammatory cytokines. In a previous study, we found that pretreatment with NAC attenuated organ dysfunction and damage, reduced the production of free radicals, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) following endotoxemia elicited by administration of lipopolysaccharide (LPS). In the present study, we tested the effects of post-treatment with NAC on the sepsis-induced change. Post-treatment imitates clinical therapeutic regimen with administration of drug after endotoxemia. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. NAC was given 20 min after LPS. Measurements of biochemical substances were taken to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, interleukin-6 (IL-6), and interleukin-10 (IL-10). LPS significantly increased blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-6, IL-10 levels and HR, and decreased MAP. Post-treatment with NAC diminished the decrease in MAP, increased the HR, and decreased the markers of organ injury (BUN, Cre, LDH, CPK, GOT, GPT) and inflammatory biomarkers (TNF-alpha, IL-6, IL-10) after LPS. We conclude that post-treatment with NAC suppresses the release of plasma TNF-alpha, IL-6, and IL-10 in endotoxin shock, and decreases the markers of organ injury. These beneficial effects protect against LPS-induced kidney, heart and liver damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound after sepsis.
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PMID:Post-treatment with N-acetylcysteine ameliorates endotoxin shock-induced organ damage in conscious rats. 1686 Mar 47

The diagnostic value of procalcitonin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-10 levels in differentiating sepsis from severe sepsis and the prognostic value of these levels in predicting outcome were evaluated and compared in patients with community-acquired sepsis, severe sepsis, and septic shock in the first 72 h of admission to the hospital. Thirty-nine patients were included in the study. The severe sepsis and septic shock cases were combined in a single "severe sepsis" group, and all comparisons were made between the sepsis (n=21 patients) and the severe sepsis (n=18 patients) groups. Procalcitonin levels in the severe sepsis group were found to be significantly higher at all times of measurements within the first 72 h and were significantly higher at the 72nd hour in patients who died. Procalcitonin levels that remain elevated at the 72nd hour indicated a poor prognosis. C-reactive protein levels were not significantly different between the groups, nor were they indicative of prognosis. No significant differences in the levels of tumor necrosis factor-alpha were found between the sepsis and severe sepsis groups; however, levels were higher at the early stages (at admission and the 24th hour) in patients who died. Interleukin-10 levels were also higher in the severe sepsis group and significantly higher at all times of measurement in patients who died. When the diagnostic and prognostic values at admission were evaluated, procalcitonin and interleukin-10 levels were useful in discriminating between sepsis and severe sepsis, whereas tumor necrosis factor-alpha and interleukin-10 levels were useful in predicting which cases were likely to have a fatal outcome.
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PMID:Evaluation of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock. 1689 29

Infection with Helicobacter trogontum, a urease-positive helicobacter isolated from subclinically infected rats, was evaluated in B6.129P2-IL10(tm1Cgn) (interleukin-10(-/-) [IL-10(-/-)]) and C57BL/6 (B6) mice. In a first experiment, IL-10(-/-) mice naturally infected with Helicobacter rodentium had subclinical typhlocolitis but developed severe diarrhea and loss of body condition with erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection with H. trogontum. A second experiment demonstrated that helicobacter-free IL-10(-/-) mice dosed with H. trogontum also developed severe clinical signs and typhlocolitis within 2 to 4 weeks, whereas B6 mice colonized with H. trogontum were resistant to disease. In a third experiment, using helicobacter-free IL-10(-/-) mice, dosing with H. trogontum resulted in acute morbidity and typhlocolitis within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported by degenerative hemograms and recovery of Escherichia coli and Proteus spp. from the livers of infected mice. Quantitative PCR data revealed that H. rodentium and H. trogontum may compete for colonization of the lower bowel, as H. trogontum established higher colonization levels in the absence of H. rodentium (P < 0.003). H. trogontum-induced typhlocolitis was also associated with a significant decrease in the levels of colonization by five of eight anaerobes that comprise altered Schaedler's flora (P < 0.002). These results demonstrate for the first time that H. rodentium infection in IL-10(-/-) mice causes subclinical typhlocolitis and that infection with H. trogontum (with or without H. rodentium) induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the normal anaerobic flora of the colon and increases the risk of sepsis.
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PMID:Rapid onset of ulcerative typhlocolitis in B6.129P2-IL10tm1Cgn (IL-10-/-) mice infected with Helicobacter trogontum is associated with decreased colonization by altered Schaedler's flora. 1698 22

The aim of this bench study was to investigate whether adenosine influences secretion of interleukin-10 (IL-O) in human whole blood culture stimulated with lipopolysaccharide. Whole blood from healthy human volunteers was mixed ex vivo in 1:1 ratio with RPMI 1640 culture medium and subsequently cultured at 37 degrees C with or without adenosine (total of 120 microM added in four aliquots over two hours) in the presence or absence of 100 ng/ml lipopolysaccharide for four and eight hours, respectively. There was only a minimal IL-10 production after four hours of culture regardless of the experimental conditions. However, lipopolysaccharide stimulated whole blood cultures with added adenosine released large amounts of IL-lO after eight hours. The response was similar whether adenosine was added before (5.99 pg/ml/10(6) leucocytes) or after (10.35 microg/ml/10(6) leucocytes) stimulation with lipopolysaccharide and interindividual variation was present. In conclusion adenosine enhances lipopolysaccharide stimulated IL-10 production in whole human blood and may contribute to the IL-10 mediated immune dysfunction in sepsis.
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PMID:Endotoxin stimulated interleukin-10 production is enhanced by adenosine. Possible key to septic shock associated immune deficiency? 1718 88

During sepsis, the anti-infectious response is closely linked to an overwhelming inflammatory process. The latter is illustrated by the presence in plasma of numerous inflammatory cytokines, markers of cellular stress (e.g. high mobility group box-1 protein), complement-derived compounds (e.g. anaphylatoxin C5a), lipid mediators, and activated coagulation factors. All mediators contribute in synergy to tissue injury, organ dysfunction, and possibly to lethality. To dampen this overzealous process, a counter-regulatory loop is initiated. The anti-inflammatory counterpart involves few anti-inflammatory cytokines (e.g. interleukin-10, transforming growth factor-beta), numerous neuromediators (e.g. adrenalin, acetylcholine), and some other factors (e.g. heat shock proteins, ligand of TREM-2, adenosine). These mediators modify the immune status of circulating leukocytes as illustrated by their decreased cell-surface expression of HLA-DR or their reduced ex vivo pro-inflammatory cytokine production in response to Toll-like receptor agonists (e.g. endotoxin, lipoproteins). However, circulating leukocytes remain responsive to whole bacteria and produce normal or even enhanced levels of anti-inflammatory cytokines. Thus, the immune dysregulation observed in sepsis corresponds to a reprogramming of circulating leukocytes.
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PMID:Determining the degree of immunodysregulation in sepsis. 1746 19

We recently showed that A(2A) adenosine receptor activation by endogenous adenosine contributes to interleukin-10 (IL-10) production in polymicrobial sepsis. Here we investigated the molecular mechanisms underpinning this interaction between adenosine receptor signaling and infection by exposing macrophages to Escherichia coli. We demonstrated using receptor knockout mice that A(2A) receptor activation is critically required for the stimulatory effect of adenosine on IL-10 production by E coli-challenged macrophages, whereas A(2B) receptors have a minor role. The stimulatory effect of adenosine on E coli-induced IL-10 production did not require toll-like receptor 4 (TLR4) or MyD88, but was blocked by p38 inhibition. Using shRNA we demonstrated that TRAF6 impairs the potentiating effect of adenosine. Measuring IL-10 mRNA abundance and transfection with an IL-10 promoter-luciferase construct indicated that E coli and adenosine synergistically activate IL-10 transcription. Sequential deletion analysis and site-directed mutagenesis of the IL-10 promoter revealed that a region harboring C/EBP binding elements was responsible for the stimulatory effect of adenosine on E coli-induced IL-10 promoter activity. Adenosine augmented E coli-induced nuclear accumulation and DNA binding of C/EBPbeta. C/EBPbeta-deficient macrophages failed to produce IL-10 in response to adenosine and E coli. Our results suggest that the A(2A) receptor-C/EBPbeta axis is critical for IL-10 production after bacterial infection.
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PMID:A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli. 1752 87

Insulin is essential for glucose homeostasis. Insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), macrophage migration inhibitory factor (MIF) and other pro-inflammatory cytokines and reactive oxygen species (ROS), enhances the synthesis of endothelial nitric oxide (eNO), and anti-inflammatory cytokines interleukins-4 (IL-4) and interleukin-10 (IL-10). In subjects who are critically ill, monocyte HLA-DR expression was significantly decreased with a concomitant increase in plasma IL-10 and IL-4 concentrations. Large increases in the plasma concentrations of TNF-alpha, IL-6, sustained increase in the expression of leukocyte CD11b/CD18, and ROS generation following surgery and infections were found to be associated with increased mortality. By virtue of its actions on pro- and anti-inflammatory cytokines and ROS, insulin may have the ability to alter HLA-DR expression in the critically ill and thus bring about its beneficial actions in sepsis/septic shock, myocardial recovery following acute myocardial infarction, improve prognosis of those who are critically ill, and suppress inflammation.
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PMID:Insulin in the critically ill with focus on cytokines, reactive oxygen species, HLA-DR expression. 1792 13

This study was performed to investigate the relationships between markers of inflammation in serum (interleukin-6 [IL-6], interleukin-10 [IL-10], and granulocyte elastase [GE]), severity of injury, and clinical outcomes, and to evaluate the predictive value of these markers for major complications and mortality. This study, which was conducted between August 2003 and May 2005, examined patients older than 16 y who were admitted to the Emergency Unit of the Uludag University Medical School within 12 h after trauma, and who had traumatic hemorrhagic shock (THS) at admission. Three groups were established: the THS group (n=20), the pure hemorrhagic shock (PHS) group (n=20), and the healthy control group (n=20). Demographic data were recorded for all subjects, and blood samples were taken for lactate, base excess, GE, IL-6, and IL-10 measurements. The Glasgow Coma Score, the Revised Trauma Score, the Injury Severity Score, the New Injury Severity Score, and the Trauma Score-Injury Severity Score were calculated; complications and final clinical outcomes were monitored. A total of 35 men and 25 women were included in the study; mean patient age was 41+/-17 y. In the THS group, scores were as follows: Revised Trauma Score, 10.2+/-2.2; Trauma Score-Injury Severity Score, 0.86+/-0.2; Injury Severity Score, 24.8+/-9.0; and New Injury Severity Score, 32.7+/-9.0. IL-6, IL-10, lactate, and base excess levels in the THS group were significantly higher than those in the PHS and healthy control groups. The serum GE level of the THS group was significantly higher than that of the healthy control group, but it did not differ significantly from that of the PHS group. Complications such as sepsis, acute respiratory distress syndrome, and multiple organ failure occurred in 50% of the THS group and in 20% of the PHS group. Mortality was 30% in the THS group and 10% in the PHS group. In the THS group, no significant differences were noted between markers of inflammation and trauma scores of patients who died and those who survived. The investigators concluded that although the levels of markers of inflammation increased in THS patients, they were inadequate for predicting mortality and the development of complications such as acute respiratory distress syndrome, multiple organ failure, and sepsis. A larger study based on the use of serial marker measurements is warranted.
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PMID:Relationships between markers of inflammation, severity of injury, and clinical outcomes in hemorrhagic shock. 1802 20

Sepsis, a systemic inflammatory response to infection, is a leading cause of death in intensive care units. Recent investigations into the pathogenesis of sepsis reveal a biphasic inflammatory process. An early phase is characterized by pro-inflammatory cytokines (e.g. tumour necrosis factor-alpha), whereas a late phase is mediated by an inflammatory high-mobility group box 1 and an anti-inflammatory interleukin-10. Inflammation aberrantly activates coagulation cascades as sepsis progresses. This dual inflammatory response concomitant with dysregulated coagulation partially accounts for unsuccessful anti-cytokine therapies that have solely targeted early pro-inflammatory mediators (e.g. tumour necrosis factor-alpha). In contrast, activated protein C, which modifies both inflammatory and coagulatory pathways, has improved survival in patients in severe sepsis. Inhibition of the late mediator high-mobility group box 1 improves survival in established sepsis in pre-clinical studies. In addition, recent advances in molecular medicine have shed light on two novel experimental interventions against sepsis. Accelerated apoptosis of lymphocytes has been shown to play an important role in organ dysfunction in sepsis and techniques to suppress apoptosis have improved survival rate in sepsis models. The vagus nerve system has also been shown to suppress innate immune response through endogenous release and exogenous administration of cholinergic agonists, ameliorating inflammation and lethality in sepsis models.
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PMID:Advances in understanding sepsis. 1828 33

This study aimed to investigate changes in the expression of human leukocyte antigen-DR (HLA-DR) on CD14+ monocytes in the peripheral blood of burn victims with delayed resuscitation in relation to the development of sepsis, and the effect of carbachol in vitro. The study population comprised 25 people with burns of at least 30% of total body surface area and delayed resuscitation, and 20 healthy volunteers as controls. Peripheral blood was collected on post-burn days 1, 3, 7, 14 and 28. When 7 participants developed sepsis, their peripheral blood was drawn on 2 consecutive days. Expression of HLA-DR on CD14+ monocytes in peripheral blood of burned participants was lower than that of controls, and fell further with the development of sepsis, when the rate and concentration of tumour necrosis factor-alpha (TNF-alpha) rose above those of controls and burned participants without sepsis. Expression of HLA-DR on CD14+ monocytes was negatively correlated with interleukin-10 (IL-10) levels on post-burn days 1, 7 and 28. In vitro, HLA-DR expression on monocytes also decreased with lipopolysaccharide (LPS) stimulation, but after treatment with carbachol, rose in a concentration-dependent manner. Thus expression of HLA-DR on CD14+ monocytes may be a useful parameter for monitoring the immune function of burn victims with and without sepsis. Carbachol significantly inhibited LPS-induced immunosuppression in human monocytes in vitro.
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PMID:Low HLA-DR expression on CD14+ monocytes of burn victims with sepsis, and the effect of carbachol in vitro. 1853 34


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