Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-6 (IL-6) is a multipotential cytokine detected in the serum of patients or experimental animals undergoing bacterial sepsis. To date, the role of IL-6 in gram-negative sepsis models has been controversial. We have used IL-6-deficient mice to investigate the role of IL-6 during virulent Escherichia coli infection and in lipopolysaccharide (LPS)-induced mortality. In this report we describe an increased susceptibility of IL-6-deficient mice to E. coli infection in terms of mortality and accumulation of viable bacteria in tissues, indicating a protective role for IL-6 during the immune response against E. coli. In contrast, mortality rates of IL-6-deficient mice and control animals undergoing LPS-induced shock did not differ, indicating that IL-6 was inconsequential for survival in this model. Furthermore, we have shown that neutrophils were crucial for resistance to E. coli in normal mice. IL-6-deficient mice were unable to efficiently induce neutrophilia in the bloodstream immediately following challenge with E. coli, in contrast to a characteristic neutrophilia induced in control animals. Prophylactic treatment of the mutant animals with recombinant IL-6 protein reverted both the deficit of neutrophilia and the accumulation of bacteria in tissues. These data clarify the role of IL-6 as protective in virulent E. coli infection and suggest that the protective effect may be at least partially mediated through neutrophils.
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PMID:Interleukin-6 is required for a protective immune response to systemic Escherichia coli infection. 875 58

The purpose of this study is to measure soluble CD14 (sCD14) levels in sera from newborn with sepsis, to compare it with other markers, and to study its evolution in Gram-negative and Gram-positive sepsis. Forty normal newborns were included (26 were full term and 14 were preterm infants), 20 babies had a positive blood culture (11 Gram-positive and 9 Gram-negative) and 16 cases were suspected of having sepsis based on clinical and laboratory findings, but a negative blood culture. Interleukin-6 (IL-6), sCD14, and tumour necrosis factor-alpha (TNF alpha) were measured by enzyme immunoassay, and fibronectin (FN) and C-reactive protein (CRP) by radial immunodiffusion. Neonates with a positive blood culture had increased levels of sCD14 (3.20 +/- 1.26 micrograms ml-1, p < 0.001), CRP (69 +/- 46 micrograms ml-1, p < 0.001) and IL-6 (134 +/- 150 pg ml-1, p < 0.001), and decreased values of FN (12.3 +/- 6.6 mg ml-1, p < 0.001). TNF alpha levels were also high (160 +/- 37 pg ml-1), but this increase was not statistically significant. Newborn infants suspected of having sepsis but a negative blood culture had similar but milder abnormalities. Soluble CD14 levels correlated with CRP values; however, there was no correlation between sCD14, TNF alpha and IL-6. Neonates with sepsis by Gram-positive bacteria had lower sCD14 levels than patients with Gram-negative sepsis (2.63 +/- 1.2 versus 4.04 +/- 1.0 micrograms ml-1, p < 0.05). In conclusion, the sCD14 level is increased in newborn infants with sepsis, and this is higher in infections by Gram-negative bacteria, suggesting a different contribution of monocyte and macrophage cells. In contrast, IL-6, TNF alpha, CRP and FN values are similar in infections by Gram-positive and Gram-negative bacteria.
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PMID:Serum levels of CD14 in neonatal sepsis by Gram-positive and Gram-negative bacteria. 881 13

Endotoxemia initiates a cytokine response that is thought to mediate the syndromes of sepsis and multiple organ failure. This study measured cytokine levels in the blood and airways of rats at critical time points during the development of lung injury induced by chronic endotoxin (LPS) infusion in the rat. Tumor necrosis factor-alpha (TNF), interleukin-1-beta (IL-1), and interleukin-6 (IL-6) were measured in the blood and bronchoalveolar lavage fluid (BALF) of endotoxemic and control animals. BALF was also studied for the percentage of neutrophil (PMN) count and chemotactic activity. Lung histology was determined at 72 h following infusion of LPS. Chronic endotoxemia of > or = 48 h but not < or = 24 h resulted in severe acute lung injury (ALI). Circulating levels of TNF and IL-1 were only transiently elevated, whereas IL-6 remained elevated in the endotoxemic rats. TNF, IL-1, and IL-6 levels in BALF were only transiently elevated. Chemotactic activity, levels of cytokine-induced neutrophil chemoattractant (CINC), and the percentage of PMN counts in BALF all increased significantly by 36 h. Other potential chemoattractants; leukotriene B4 and transforming growth factor-beta were not elevated in BALF. In conclusion, severe ALI requires a minimum of 48 h LPS infusion in this model and is associated with high levels of circulating IL-6, increased CINC activity, and an increased percentage of PMN count in BALF. Local inflammatory events may be as important as the systemic cytokine milieu in mediating ALI. The signal for these local events does not appear to depend solely on the transient elevations of circulating TNF and IL-1 at the onset of endotoxemia, although sustained high levels of IL-6 may be important.
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PMID:Acute lung injury in endotoxemic rats is associated with sustained circulating IL-6 levels and intrapulmonary CINC activity and neutrophil recruitment--role of circulating TNF-alpha and IL-beta? 882 83

Interleukin-6 (IL-6), a cytokine involved in the pathogenesis of sepsis and septic shock, and lymphocyte subpopulations were measured in blood circulation of patients receiving sodium nitroprusside (SNP) for induction of hypotension. The aim of this study was to evaluate whether this procedure influences distribution of lymphocyte subsets and IL-6 response. 30 patients of ASA physical status I and II scheduled for nose-septum correction were randomly assigned to the SNP- or control group (without SNP). Patients were anaesthetized with fentanyl, etomidate and isoflurane in 66% nitrous oxide. SNP was administered continuously during 60 min and mean arterial blood pressure was reduced to 50 mmHg. Before and after induction of anaesthesia, 60 min after the beginning of the operation (end of SNP-infusion) and on the first postoperative day, IL-6 plasma concentrations were determined by ELISA. The percentages of B-, T-lymphocytes, T-helper, T-suppressor cells and HLA-DR positive (activated) T-lymphocytes were examined by direct immunofluorescence using monoclonal antibodies. On the first day after surgery IL-6 plasma concentrations were significantly elevated in the SNP-group compared to preoperative values. In this group the values were higher than in control patients [30.5 (10.9-47.5) pg/ml vs. 17.4 (8.5-21.5) pg/ml]. The percentage of HLA-DR positive T-cells was 25.8 +/- 4.9% in the patients with SNP on the first postoperative day; it was significantly higher than in control patients [16.5 +/- 3.7%]. We conclude that SNP-administration increases percentage of activated T-cells and IL-6 secretion.
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PMID:Increase of interleukin-6 plasma concentrations and HLA-DR positive T-lymphocytes after hypotensive anaesthesia with sodium nitroprusside. 884

In this study the ability of soluble interleukin-6 receptor (sIL-6R) to stimulate interleukin-6 (IL-6) synthesis in human fibroblasts is described. It was found that sIL-6R, in combination with endogenous or exogenous IL-6, markedly upregulated IL-6 synthesis. These data suggest that increased IL-6 production after stimulation by either interleukin-1 or tumor necrosis factor-alpha would result in complex formation with sIL-6R, rapid uptake, and further synthesis of this cytokine. Furthermore, it would explain the decrease in sIL-6R plasma levels observed in patients suffering from sepsis.
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PMID:Effect of soluble interleukin-6 receptor on interleukin-6 synthesis in human skin fibroblasts. 887 15

We evaluated the effect of interleukin-6 (IL-6) on the production of prostacyclin (PGI2) by cultured human pulmonary artery smooth muscle cells (HPASMC). Incubation of these cells for up to 48 h with IL-6 led to a dose- and time-dependent decrease in the concentration of PGI2 in the culture medium. The incubation of HPASMC with 10 micrograms/ml of lipopolysaccharide (LPS), 200 U/ml of IL-1 beta, or 500 U/ml of TNF alpha for 24 hr significantly increased the concentration of PGI2 in the medium. However, the addition of IL-6 to a medium containing LPS, IL-1 beta, or TNF alpha significantly inhibited the stimulatory effect of those substances on PGI2 production. Such inhibition was closely related to the concentration of IL-6. IL-6 may counteract the roles of LPS and of other cytokines on the regulation of pulmonary vascular tension in endotoxin- and cytokine-mediated disorders such as sepsis and the acute respiratory distress syndrome (ARDS).
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PMID:Inhibitory effects of interleukin-6 on release of PGI2 by cultured human pulmonary artery smooth muscle cells. 888 Aug 95

We tested the hypothesis that, during sepsis, the balance of pro- and anti-inflammatory cytokines is related to severity and survival. Cecal ligation and puncture (CLP) with a large (18-gauge)-, intermediate (21-gauge)-, or small (26-gauge)-diameter needle, or sham laparotomy, was performed on outbred CD-1 mice. Concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 were measured (by enzyme-linked immunosorbent assay) in serum, peritoneal lavage fluid, and liver and lung samples at 4, 8, 24, 48, and 96 h. As the diameter of the CLP needle decreased, the mortality rate decreased (at 48 h: large, 80%; intermediate, 40%; small, 20%; P < 0.05), the TNF-alpha and IL-6 concentrations decreased, and the time-to-peak TNF-alpha expression increased. In contrast, IL-10 concentration increased compared with baseline (serum at 24 h: large, 2.3-fold +/- 1.6-fold; intermediate, 2.0-fold +/- 0.5-fold; small, 49.9-fold +/- 8.3-fold; P < 0.05). Administration of IL-10 (5 microg, intraperitoneal) prior to CLP decreased mortality (P < 0.001). Administration of polyclonal anti-IL-10 serum prior to CLP (0.5 ml intraperitoneal) had the opposite effect and increased mortality (P < 0.001) and TNF-alpha, IL-6, and TNF-alpha mRNA expression compared with controls. Thus, severe sepsis is associated with a largely unopposed inflammatory response, and a largely unopposed inflammatory response (with anti-IL-10) results in severe sepsis and death. Less severe sepsis is associated with greater anti-inflammatory mediator expression, and greater anti-inflammatory mediator expression (with IL-10) results in less severe sepsis. Thus, the balance of inflammatory mediators is related to the severity and mortality of murine sepsis.
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PMID:Balance of inflammatory cytokines related to severity and mortality of murine sepsis. 889 Feb 33

Cytokines play a major role in the pathophysiology of sepsis and septic shock. Using enzyme immunoassays the acute serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and leukemia inhibitory factor (LIF) were investigated in 90 patients with positive blood cultures and clinical signs of infection. In 27 patients samples were obtained on admission, after 1, 4, 12, 18, and 24 h, and then daily. The acute serum levels of IL-6, TNF-alpha, G-CSF, and IL-8 were significantly higher among patients with severe sepsis. Patients with Gram-negative infection had significantly higher levels of TNF-alpha on admission than did patients with Gram-positive infections (p = 0.0008). The levels of IL-6, G-CSF and, to some extent, TNF-alpha decreased rapidly in survivors within the first 24 h of admission to hospital and institution of treatment. LIF was detected in 8/90 in both survivors and nonsurvivors.
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PMID:Dynamics of blood cytokine concentrations in patients with bacteremic infections. 889 5

This study reports the predictive value, in septic patients, of septic shock at presentation (SS factor) alone and in combination with multiple markers, using survival of the sepsis episode as the outcome measure. The SS factor correctly predicted the outcome in 53/68 (78%) of patients in this study. The Acute Physiology and Chronic Health Evaluation II Score (APACHE II or APII) and interleukin-6 (IL-6) and IL-6 soluble receptor (IL-6sR) concentrations were evaluated in combination with the SS factor in the same 68 patient population which was randomly divided into design (# = 50) and test groups (# = 18). Two iterations of an algorithm were evaluated using randomized patient groups corresponding to those producing the best (Group A) and worst (Group B) performance using a neural network. The four-input algorithm (APII, IL-6, IL-6sR, SS factor) correctly classified 16/18 (89%, Group A) and 14/18 (78%, Group B) of patients in the test subset. The corresponding four-input neural network model (10 iterations) correctly classified 61 to 89% of the 18 patients in the 10 test subsets.
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PMID:Multiparameter models for the prediction of sepsis outcome. 890 16

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.
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PMID:Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia. 893 27


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