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)

Interleukin (i.l.)-8 levels in serial serum samples of 10 burned patients were analysed. The total body surface areas (TBSAs) of the burn injury ranged 30 to 85 per cent. Of these ten patients, five recovered and the other five, who were septic, died. On admission at about 5-13 h postburn, one of the five survivors and two of the non-survivors had serum IL-8 levels higher than 18.1 pg/ml, which is the detection limit of the IL-8 assay kit. The serum IL-8 values of six healthy laboratory personnel included in the present study were all less than 18.1 pg/ml. Afterwards, an initial peak serum IL-8 response was detected within 2-4.5 days postburn. Significant differences in the peak serum IL-8 levels were not found between patients with TBSAs of greater or less than 50 per cent and patients who survived or expired from burn injury. In the survivors, serum IL-8 remained low, whereas IL-8 increased markedly, starting at about one week postburn in four of the five non-survivors with confirmed sepsis. Significant differences in the maximum serum IL-8 levels were detected between patients who recovered vs. those who died from the thermal injury. In conclusion, the results showed that there was an increase in serum IL-8 postburn. Serum IL-8 was significantly higher in the septic patients, who all died. This cytokine may play a significant role in the pathophysiology of sepsis in burned patients.
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PMID:Changes in levels of serum IL-8 in burned patients. 956 23

An in vitro system composed of a plasma separation membrane coupled with natural (charcoal) or synthetic (Amberlite, Amberchrome) types of sorbents was evaluated for the simultaneous removal of proinflammatory cytokines (TNF-alpha, IL-1 beta and IL-8) and cytokine antagonists [interleukin (IL)-1 receptor antagonist (IL-1Ra), soluble tumor necrosis factor-alpha (TNF-alpha) receptor I and II (sTNFR I and II)] in whole blood spiked with bacterial lipopolysaccharide (LPS). These studies showed that plasma filtration rather than ultrafiltration significantly increased the clearance of all cytokines, particularly TNF-alpha, and the synthetic (Amberlite-type of resin) but not natural (uncoated charcoal) membrane could extensively absorb almost 100% of plasma filtered IL-Ra, IL-1 beta and IL-8, but only 40% of TNF-alpha. Other synthetic (Amberchrome) membranes could also effectively (80%) remove TNF-alpha. In the complex scenario of sepsis, the simultaneous removal of excess proinflammatory and/or immunomodulatory mediators may play a role in reducing the hemodynamic alterations, thus resulting in enhanced patient survival. Whether this occurs in the human setting awaits the results of an ongoing clinical investigation.
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PMID:Continuous plasma filtration coupled with sorbents. 957 1

An in vitro model for the study of sepsis mediators was used to investigate the effects of two different lipopolysaccharides (LPS), a smooth (LPS-S) and a rough (LPS-R) type, on the release of chemokines (IL-8 and MIP-1 alpha) and cytokines (TNF alpha, IL-1 beta, IL-1ra and IL-10) from human whole blood samples. TNF alpha level increased significantly vs. control, at 4 h and 8 h after the challenge with smooth and rough type of LPS respectively. Concentrations of the two chemokines studied, IL-8 and MIP-1 alpha, were significantly elevated following stimulation by both LPS, and reached concentrations significantly different from controls at 4, 8 and 24 h. After 24 h of incubation both LPS produced a significant IL-10 increase, although such change was more substantial with the rough type. Present data suggest an early and maintained release of chemokines regardless of the type of LPS used and often in absence of a significant increase in primary pro-inflammatory cytokines.
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PMID:Kinetics of IL-8, MIP-1 alpha, TNF alpha, IL-1 beta, IL-1ra and IL-10 in human whole blood samples triggered by smooth and rough LPS. 957 36

We have previously shown that an anticoagulant could attenuate inflammation in animal models of sepsis with disseminated intravascular coagulation (DIC) and that coagulation activation of human whole blood ex vivo results in a proinflammatory cytokine response. The current studies were performed to better understand mechanisms for the blood cell cytokine response and extend the investigation of such a response to endothelial cells as likely contributors to a vascular inflammatory response. Utilizing cell separation techniques, it was determined that the whole blood IL-8 response to coagulation activation or thrombin, specifically, was mediated by CD14+ monocytes. Moreover, thrombin was observed to stimulate both IL-8 and IL-6 production in cultured mononuclear cells. Analyses of the effects of coagulation activation and thrombin were extended to cultured human endothelial cells, and a similar cytokine response was observed. Thrombin catalytic activity appeared essential, since hirudin reduced thrombin-stimulated proinflammatory cytokine production in cultured monocytes and endothelial cells and prothrombin only weakly mimicked the thrombin response. The endothelial cell IL-8 and IL-6 response to thrombin could be mimicked by the thrombin receptor agonist peptide (TRAP), implicating a functional role of the classic thrombin receptor. Altogether, the results facilitate a better understanding of potential proinflammatory vascular responses to coagulation activation.
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PMID:Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation. 959 Feb 65

Enzymes and other factors secreted by degranulating neutrophils (polymorphonuclear leukocytes, PMNs) mediate endothelial injury, thrombosis, and vascular remodeling. In bacteremia and sepsis syndrome and their consequent complications (including acute respiratory distress syndrome and systemic ischemia-reperfusion resulting from septic shock), neutrophil degranulation is an important mechanism of injury. In related studies, we found that human endothelial cells regulate neutrophil degranulation and that inflammatory cytokines induce synthesis of degranulating factors by human endothelial cells. Here we show that lipopolysaccharides (LPS) from gram-negative bacteria were the most potent agonists for release of degranulating activity by endothelial cells when compared to several cytokines and stimulatory factors. LPS also induced the release of degranulating signals for PMNs from a human endothelial cell line, EA.hy 926. Interleukin 8 (IL-8) is synthesized by endothelial and EA.hy 926 cells in response to LPS and induces neutrophil degranulation. However, complementary strategies using receptor desensitization, translation of messenger RNA by Xenopus laevis oocytes, and purification and analysis of factors from conditioned supernatants demonstrated that degranulating factors distinct from IL8 are generated in response to LPS. The characteristics of a partially purified degranulating factor isolated from conditioned supernatants distinguished it from known chemokines and other factors that induce PMN degranulation and are generated by endothelial cells in response to LPS. Thus, cultured human endothelial cells and endothelial cell lines synthesize several unique signaling molecules that can trigger neutrophil granular secretion. If produced in vivo in response to LPS or other pathologic agonists, these degranulating signals may activate PMNs in combination or in sequence, initiating or propagating vascular damage.
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PMID:Bacterial lipopolysaccharide induces endothelial cells to synthesize a degranulating factor for neutrophils. 961 46

The impact of antibiotics on total endotoxemia and circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe bacteremic sepsis or septic shock due to gram-negative species was investigated. Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and 4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0 (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL; interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4 (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that endotoxemia is not increased by antibiotherapy of severe gram-negative bacteremia.
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PMID:Circulating endotoxin during initial antibiotic treatment of severe gram-negative bacteremic infections. 965 53

The objective of the investigation was to evaluate the possible use of selected cytokines and cytokine receptors in the early diagnosis of postoperative intraabdominal sepsis. The investigation was focused on the dynamics of plasma levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on model operations (resection of large bowel and resection of pancreas). These two groups were compared with values recorded in patients with sepsis and with healthy subjects. Based on the assembled results the authors recommend to use for postoperative investigations the first 48 hours and to follow up the following parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators differentiate sufficiently specifically incipient sepsis from an uncomplicated postoperative condition. During the subsequent period, i.e. more than 48 hours after surgery, it is useful to include in the examination pattern also some acute stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which differentiate sepsis between the 3rd and 5th day after surgery.
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PMID:[The significance of cytokines in the early diagnosis of postoperative intraabdominal sepsis]. 965 57

Injured patients with Candida antigen titres have increased mortality due to sepsis. Polymorphonuclear leucocytes (PMNs) from injured patients with elevated Candida antigen titres demonstrate impaired function against Candida albicans growth when compared with PMNs from injury matched controls. To determine if PMN dysfunction is global, PMNs from patients with positive Candida antigen titres were evaluated for their ability to activate the anticandidal function of normal PMNs (autocrine activation) and to produce tumour necrosis factor (TNF) and interleukin 8 (IL8), known activators of PMN anticandidal function, this study demonstrates that the PMN dysfunction is not global, as PMN cytokine production and autocrine activation remain intact.
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PMID:Intact autocrine activation and cytokine production by PMNs from injured adults with elevated Candida antigen titres. 965 79

TNF is produced by monocytes/macrophages in response to endotoxin, which may lead to septic shock. TNF stimulates neutrophil adherence, degranulation, and superoxide production, but inhibits neutrophil migration. A mitigating anti-inflammatory effect can be experimentally induced in septic shock by TNF blockers, such as pentoxifylline, and is also suggested for treatment with hrG-CSF. With regard to the combination of pentoxifylline and hrG-CSF, the purpose of this investigation was to explore whether and in what way the effects of hrG-CSF and pentoxifylline interact with each other in neutrophils. To this end, we studied the effects of pentoxifylline on TNF- and G-CSF-induced modulation of neutrophil chemotaxis and O2 release. TNF and G-CSF decreased directed migration of neutrophils to FMLP or IL-8. High-dose pentoxifylline (1 mM) was able to counteract the effect of TNF but not that of G-CSF on neutrophil migration. In the presence of pentoxifylline, TNF and G-CSF were unable to stimulate respiratory burst. In contrast, pre-exposure of cells to pentoxifylline followed by washing increased the priming effect of TNF or hrG-CSF on neutrophil respiratory burst activity. The methylxanthine derivative by itself showed no effect on spontaneous and fMLP-stimulated O2 release by neutrophils. Stimulation of neutrophil respiratory burst by pentoxifylline may not be detectable in the presence of pentoxifylline due to its known oxygen-radical scavenging function. Results suggest that by blocking the inflammatory action of TNF on neutrophils, pentoxifylline may diminish endothelial cell damage caused by inhibited neutrophil chemotaxis. On the other hand, since transiently present pentoxifylline may enhance the respiratory burst activity of TNF- or hrG-CSF-primed neutrophils, concomitant administration of pentoxifylline and hrG-CSF to patients with SIRS/sepsis might diminish beneficial effects of the latter and additional deleterious effects might occur.
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PMID:Pentoxifylline differentially regulates migration and respiratory burst activity of the neutrophil. 970 61

Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects on septic multiple organ dysfunction in clinical and experimental studies. It was the aim of this study to determine whether continuous long-term AT III supplementation alters the systemic inflammatory response in patients with severe sepsis. In a prospective study, 29 surgical patients with severe sepsis were randomly assigned to receive either conventional intensive care treatment (n = 15, control group) or additional AT III supplementation to achieve a plasma AT III activity >120% during a 14 day study period (n = 14, AT III group). Plasma concentrations of interleukin (IL)-6 and IL-8 and of the circulating soluble adhesion molecules sICAM-1 and sE-selectin, as well as of PMN elastase, were determined daily. Additionally, total leukocyte count and C-reactive protein (CRP) were measured daily, and body temperature was registered. Compared to control patients, a down-regulation of plasma IL-6 was observed in the AT III group (p < or = .01). AT III supplementation prevented the continuous increase in sICAM-1 plasma concentration observed in control patients and led to a significant fall in soluble sE-selectin and CRP concentration (p < or = .01). This fall corresponded to a down-regulation of body temperature over time (p < or = .01). There was no AT III effect on IL-8, PMN-elastase concentration, or total leukocyte count. Our results show that long-term AT III supplementation attenuates the systemic inflammatory response in patients with severe sepsis. The down-regulation of IL-6 may also explain the fall in endothelium-derived adhesion molecules and may represent the molecular basis by which AT III exerts its beneficial effects on organ function.
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PMID:Effect of antithrombin III supplementation on inflammatory response in patients with severe sepsis. 972 74


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