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)

The function of vascular endothelial cells is to adjust blood vessel tonus, which contributes to maintaining homeostasis within blood vessels. However, inflammatory cytokines are produced in response to invasion by stimulating vascular endothelial cells and sometimes lead to shock or multiple organ failure. In the present study, we assessed cytokines in sepsis and septic shock, and various factors that are said to have a damaging effect on vascular endothelium. Endotoxin was measured by endotoxin-specific methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) were measured by enzyme-linked immunosorbent assay (ELISA). Endothelin-I was measured by radioimmunoassay (RIA). Nitric oxide was measured as metabolites of nitrite and nitrate oxides (NOx) by a method based on the Griess method. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (PGF 1 alpha) were both measured by RIA. All of the factors except endotoxin were significantly higher in the septic shock group than in the non-shock group and significantly higher in the non-survivor group than in the survivor group. Significant correlations were also found between endothelin-1 and NOx and between TXB2 and PG1 alpha. Significant correlations were also found between TNF-alpha and IL-6, endothelin-1, NOx and TXB2, but no significant correlations were detected between any of them and endotoxin. In serious diseases such as septic shock, the vascular endothelial constricting factors, endothelin and TXB2, and the blood vessel relaxing factors NOx and PGF1 alpha increase almost simultaneously. This suggests that the body's regulating mechanisms are disrupted in these serious conditions. The results of this study also suggest that inflammatory cytokines may be involved in stimulating the production of these factors.
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PMID:Functional modification of vascular endothelial cells by cytokines during septic shock. 894 12

Blood levels of various cytokines were determined in patients with burn injury immediately after the accident, and the relationship between cytokines and morbid condition was investigated. There was almost no marked elevation of cytokines in the early stage of burn injury. Throughout the entire course, tumour necrosis factor alpha, interleukin 6 and interleukin 8, as cytokines, showed high levels in patients with burn injury associated with sepsis and those who died. These levels well reflected the severity in the phase complicated with sepsis.
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PMID:Plasma cytokine levels in patients with severe burn injury--with reference to the relationship between infection and prognosis. 898 34

The acute phase response (APR) that follows injury or infection is characterized by a decrease in serum zinc concentrations, which we hypothesized benefits the host. Additionally, we proposed that preventing this decline by supplementing zinc would result in an exaggerated APR as indicated by elevated temperatures, increased serum cytokine concentrations, interleukin 6 and the acute phase protein (ceruloplasmin). A prospective, randomized, double-blinded, clinical trial was conducted. Patients on home parenteral nutrition with a diagnosis of catheter sepsis and patients with a diagnosis of pancreatitis, also on total parenteral nutrition (TPN), were recruited for the study. Following enrollment, block randomization was used to assign patients to receive 0 mg (n = 23) or 30 mg (n = 21) of zinc per day for the first 3 d of TPN. Blood samples for measurement of serum zinc, copper, ceruloplasmin and interleukin-6 were obtained upon enrollment and on d 1 through 3 of TPN. The highest temperatures reported on these days in the medical record were also recorded. Repeated measures ANOVA was used to determine differences in the primary outcome variables over time. No significant differences between groups were observed in serum interleukin-6 or ceruloplasmin concentrations. A significantly higher (P = 0.035) temperature was observed in the zinc-supplemented group compared with the control group on d 3 of parenteral nutrition. We conclude that parenteral zinc supplementation in patients experiencing a mild APR resulted in an exaggerated APR as evidenced by a significantly higher febrile response.
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PMID:Parenteral zinc supplementation in adult humans during the acute phase response increases the febrile response. 904 May 47

The aim of the present study was to investigate the relationship between the levels of pro-inflammatory [interleukin 6 (IL-6), IL-8, tumour necrosis factor alpha (TNF-alpha)], anti-inflammatory cytokines [IL-10, soluble TNF receptor type I (TNFsrI), TNFsrII], and the production of nitric oxide (NO) during a 1-week period in 23 patients with severe sepsis. The highest levels of pro-inflammatory cytokines and nitrate, the stable metabolite of NO, were found during the first day after inclusion and gradually declined thereafter. Detectable levels of IL-10, TNFsrI and TNFsrII were present in all patients at study entry but did not significantly change during the study period [analysis of variance (MANOVA); P > 0.05]. Serum nitrate levels correlated significantly with both pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) as well as anti-inflammatory cytokines (IL-10, TNFsrI, TNFsrII). Serum nitrate levels over time were higher in patients with positive blood cultures (n = 4) (MANOVA; P < 0.005), as compared to patients without proven bacteraemia. These data support the concept of an acute phase of sepsis that is characterized by an excess of pro-inflammatory cytokines, while anti-inflammatory cytokines are predominantly present during the secondary phase. The present findings indicate that pro-inflammatory cytokines are related to the induction of excessive NO production during the first phase of sepsis and that reduction of NO production occurs during the secondary phase. This may suggest that anti-inflammatory cytokines are able to diminish the production of NO in patients with severe sepsis.
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PMID:Relation between pro- and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis. 907 65

Meningococcal sepsis results partly from overproduction of host cytokines after macrophages interact with endotoxin. To obtain less toxic and highly immunomodulatory meningococcal endotoxins for prophylactic purposes, we investigated the relationship between endotoxicity and immunomodulatory activity of several endotoxin preparations from Neisseria meningitidis group B. Using the D-galactosamine-sensitized mouse model to determine endotoxin lethality, we found that the toxicity of purified lipooligosaccharide (LOS) from M986, a group B disease strain, was three to four times higher than those of purified LOSs from the noncapsulated strains M986-NCV-1 and OP-, the truncated-LOS mutant. The LOSs of outer membrane vesicles (OMVs) and detergent-treated OMVs (D-OMVs) from the three strains were 2 to 3 and over 300 times less toxic than the purified LOSs, respectively. Intraperitoneal administration of these preparations induced production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in serum 2 h after injections. However, repeated doses of low- and high-toxicity preparations induced lower amounts of TNF-alpha and IL-6, i.e., LOS tolerance. Injection of mice with low doses of LOS was as effective as injection with high doses in inducing tolerance. Peritoneal macrophages from tolerant mice pretreated with either high- or low-toxicity LOS preparations produced only a fraction of the amounts of TNF-alpha and IL-6 produced by control groups in response to LOS ex vivo. Despite tolerance to LOS induced by pretreatment with reduced-toxicity preparations, killing of N. meningitidis M986 by macrophages from these animals was enhanced. Protection was achieved when mice treated with LOS, and especially that of D-OMVs, were challenged with live N. meningitidis. The least toxic LOS, that in D-OMVs, was most effective in inducing hyporesponsiveness to endotoxin in mice but protected them against challenge with N. meningitidis. No inevitable link between toxicity and host immune modulation and responses was shown. Our results show that LOS is responsible for both toxicity and immunomodulation. When LOS is tightly associated with outer membrane proteins in D-OMV, it reduces toxicity but enhances beneficial effects compared to results with its purified form. Thus, systematic and critical evaluation of D-OMVs as adjuvants or as portions of group B meningococcal vaccines may help improve survival and outcome in meningococcal sepsis.
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PMID:Modulation of the biological activities of meningococcal endotoxins by association with outer membrane proteins is not inevitably linked to toxicity. 912 92

Individuals with a consistently lower immune response may be more susceptible to infection but less prone to autoimmune disease or severe sepsis. The molecular mechanisms determining the low responder status are, however, unclear. We have screened 60 male donors for tumour necrosis factor (TNF) protein levels after stimulation of monocytes with lipopolysaccharide (LPS). Among these we identified three donors each that consistently had a level of less than 20% (low responders; LR) or of more than 80% (high responders; HR) of the maximum response seen in this population. Northern blot analysis of TNF mRNA after LPS stimulation revealed lower transcript levels in LR. Half life determination after actinomycin D blockade showed a similar decay rate for LR and HR and after blockade of degradation by cycloheximide treatment mRNA levels increased but LR remained lower compared to HR. These data indicate that the lower TNF mRNA levels in LR are not due to a more rapid mRNA degradation but rather a result of lower transcription. Transcripts for interleukin 6 (IL-6) were also low in LPS-stimulated monocytes of LR. Because expression of the LPS receptor CD14 was similar in LR and HR monocytes, our data suggest that differences in signal transduction account for the LR and HR phenotype.
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PMID:TNF gene expression in monocytes of low and high responder individuals. 912 9

Recent evidence indicates that inflammatory cytokines are involved in changes of blood glucose concentrations and hepatic glucose metabolism in infectious diseases, including sepsis. However, little is known regarding how cytokines interact with glucoregulatory hormones such as insulin. The objective of the present study is to investigate if and how cytokines influence insulin-stimulated glycogen metabolism in the liver. Interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) markedly inhibited the increase of glycogen deposition stimulated by insulin in primary rat hepatocyte cultures; however, tumor necrosis factor alpha had no effect. Labeling experiments revealed that both cytokines counteracted insulin action by decreasing [14C]-glucose incorporation into glycogen and by increasing [14C]-glycogen degradation. Furthermore, it was discovered that IL-1beta and IL-6 inhibited glycogen synthase activity and, in contrast, accelerated glycogen phosphorylase activity. In experiments with kinase inhibitors, serine/threonine kinase inhibitor K252a blocked IL-1beta- and IL-6-induced inhibitions of glycogen deposition, as well as glycogen synthase activity, whereas another kinase inhibitor staurosporine blocked only IL-6-induced inhibition. Tyrosine kinase inhibitor herbimycin A blocked only IL-1beta-induced inhibition. These results indicate that IL-1beta and IL-6 regulate insulin-stimulated glycogen synthesis through different pathways involving protein phosphorylation in hepatocytes. They may mediate the change of hepatic glucose metabolism under pathological and even physiological conditions by modifying insulin action in vivo.
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PMID:Interleukin 1beta and interleukin 6, but not tumor necrosis factor alpha, inhibit insulin-stimulated glycogen synthesis in rat hepatocytes. 958 83

The aim of this study was to monitor plasma interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), levels in patients with sepsis, septic shock and multiple organ dysfunction syndrome admitted to the intensive care unit. The patients obtained adequate supportive therapy. Plasma samples were taken upon admission, then on days 1, 2, and 5 following admission. IL-6 and TNF-alpha levels were determined using bioassays (7TD1 and WEHI-164.13 indicator cell lines, respectively). The results showed that the kinetics of the cytokine release in septic patients differed significantly between survivors and nonsurvivors. In survivors IL-6 concentrations were initially high, fell down rapidly on day 1 after admission, and persisted very low throughout the monitoring time. In contrast, relatively low IL-6 levels in the nonsurvivors, registered upon admission, rose significantly with peak values on day 3 of observation, declining thereafter. TNF-alpha levels were initially higher in survivors than in nonsurvivors, declined on day 1 following admission, and on day 5 they were higher than the initial values. In nonsurvivors, on the other hand, the starting concentrations of TNF-alpha were much lower than in survivors with a peak on day 3 with a tendency to fall on day 7. The profiles of cytokine production by traumatic patients (90% survivors) revealed low and progressively diminishing levels of IL-6, contrasting with constantly increasing concentrations of TNF-alpha within the monitoring period. We conclude that high IL-6 levels in septic patients accompanied by high TNF-alpha levels may indicate bad prognosis. In contrast, rapidly diminishing serum IL-6 levels, even in the presence of high TNF-alpha levels, could indicate a very good chance for survival. Similar conclusion can be drawn from the monitoring of cytokine production in traumatic, nonseptic patients since almost all of them recovered. We also speculate that TNF-alpha presence in circulating blood is essential for regeneration of tissues and wound healing.
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PMID:Immunological status of septic and trauma patients. I. High tumor necrosis factor alpha serum levels in septic and trauma patients are not responsible for increased mortality; a prognostic value of serum interleukin 6. 959 83

In this study the authors assessed plasma leukaemia inhibitory factor (LIF), interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) concentrations in 28 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Plasma IL-6 levels increased during ECC, reaching a 33-fold increase 6 h after surgery as compared to pre-operative values. In contrast, plasma sIL-6R and LIF concentrations did not vary significantly during cardiac surgery. Thus, LIF is not implicated in the haematological changes and in the inflammatory syndrome observed after CABG. Despite the fact that LIF and IL-6 exhibit several common biological activities, the production of these two cytokines is differently regulated during cardiac surgery with ECC. Plasma IL-6 levels increased during cardiac surgery while sIL-6R levels did not changed. These data contrast with the decreased sIL-6R concentrations with concomitantly high IL-6 levels in patients with sepsis syndrome suggesting that inflammatory reactions in sepsis and after cardiopulmonary bypass are triggered by different mechanisms.
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PMID:Plasma leukaemia inhibitory factor, interleukin 6 and soluble interleukin 6 receptor levels during cardiopulmonary bypass with extracorporeal circulation. 961 76

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.
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PMID:Complement activation in relation to capillary leakage in children with septic shock and purpura. 978 43


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