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 multiorgan failure syndrome caused by group A streptococci (GAS) designated streptococcal toxic shock syndrome (STSS) is believed to be mediated by cytokines induced by superantigens. In order to study the relationship between superantigen production, cytokine levels in patient sera, and clinical GAS manifestation we examined acute-phase sera and strains from 25 patients with GAS bacteremia. The patients had various disease manifestations, including STSS (44%), erysipelas (28%), septicemia (24%), wound infections (16%), and pneumonia (12%). Serotype T1M1 dominated, representing 56% of the isolates, but also strains of other serotypes were identified. The strains were found to produce the streptococcal pyrogenic exotoxins (Spe) A, B, and F, as determined by immuno-blot analyses. There was no difference in amounts of toxin produced between strains isolated from patients with different manifestations of disease. Levels of TNF alpha, IL1 alpha, IL6, IL8, and IFN gamma in acute-phase sera were determined by use of ELISA and RIA assays. The analyses showed higher levels of IL6 in sera from patients with STSS than in sera from patients with bacteremia without shock. TNF alpha was elevated in sera from patients with STSS, as compared to sera from patients with uncomplicated pharyngotonsillitis. No increase in the levels of IL1 alpha, IL8, and IFN gamma could be found in the patient sera and there was no difference in the level of those cytokines between the various patient categories.
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PMID:Correlation between serum TNF alpha and IL6 levels and severity of group A streptococcal infections. 766 74

Pseudomonas aeruginosa infections are commonly observed in sepsis, burns, as well as cystic fibrosis (CF). Among the professional phagocytes neutrophils and monocytes are recruited by various chemotactic factors from the cellular environment. Although they provide the first line of host defense excessive neutrophil accumulation seems to be a major cause of pathogenesis during P. aeruginosa infection. Interleukin-8 (IL-8) represents one important chemoattractant for professional phagocytes. To evaluate IL-8 releasability by phagocytes in the context of P. aeruginosa infection and especially of CF, we stimulated human polymorphonuclear neutrophilic granulocytes (PMN) and peripheral blood mononuclear cells (PBMC) as a source for monocytes with clinical P. aeruginosa isolates, with mucoid P. aeruginosa strain (CF3M) and its nonmucoid revertant (CF3), and with purified P. aeruginosa mucoid exopolysaccharide (alginate). A significant increase in IL-8 release as compared to unstimulated cells was observed after an incubation time of 90 min for PMN and after 60 min for PBMC which increased (PMN: up to 60-fold; PBMC: up to 40-fold) over time (up to 4 h). In contrast of PBMC, when PMN were studied, intracellular IL-8 exceeded the IL-8 release in unstimulated as well as in stimulated cells by up to 10-fold. All clinical P. aeruginosa isolates, independent of the clinical source, induced IL-8 release from human PBMC and PMN in a dose- and time-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of Pseudomonas aeruginosa on interleukin-8 release from human phagocytes. 771 53

Interleukin 10 (IL-10) suppresses the production of proinflammatory cytokines in vitro and in murine models of endotoxemia and has been suggested as a candidate for treatment of bacterial septicemia. To investigate the role of IL-10 in meningococcal disease, a sandwich IL-10 enzyme-amplified sensitivity immunoassay was used to quantitate IL-10 in serum and cerebrospinal fluid samples from 41 patients with meningococcal bacteremia or meningitis with or without septic shock. High levels of IL-10 were demonstrated in sera from patients with meningococcal septic shock (mean, 21,221 pg/ml; range, 25 to 64,500 pg/ml). All cases involving fatalities had IL-10 levels in serum of > or = 1,000 pg/ml (mean, 23,058 pg/ml; range, 1,000 to 64,500 pg/ml). Patients with meningococcal meningitis without septic shock had comparably low concentrations of IL-10 in serum (mean, 119 pg/ml; range, 0 to 1,050 pg/ml) but exhibited compartmentalized release of IL-10 in cerebrospinal fluid. Concentrations of IL-10 in serum were positively correlated with the previously reported concentrations of tumor necrosis factor alpha, IL-6, and IL-8 in serum in the same patients. We conclude that IL-10 is extensively activated along with the proinflammatory cytokines during the initial phase of meningococcal septic shock and that IL-10 is associated with fatality in meningococcal disease.
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PMID:High levels of interleukin 10 in serum are associated with fatality in meningococcal disease. 776 88

The chemokine monocyte chemotactic protein 1 (MCP-1) is a cytokine with chemotactic activity specific for mononuclear phagocytes. To investigate the possible involvement of MCP-1 in the pathogenesis of sepsis, its course was studied in baboons challenged intravenously with a sublethal or lethal dose of Escherichia coli. Levels of MCP-1 started to increase in both groups of animals 2 h after injection of E. coli, reaching peak levels 4 and 6 h after a sublethal (186 +/- 21 ng/mL) or a lethal (213 +/- 24 ng/mL) dose, respectively. Levels of MCP-1 correlated significantly with plasma levels of another chemokine, interleukin-8 (IL-8; r = .826. P < .001), suggesting that common stimuli mediate the release of both cytokines in this model.
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PMID:Monocyte chemotactic protein 1 is released during lethal and sublethal bacteremia in baboons. 776 8

Septic shock is the major cause of treatment-related death in patients with acute myelogenous leukaemia (AML) undergoing intensive chemotherapy. Interleukins (IL)-1 beta, -6, -8, and tumour necrosis factor alpha (TNF-alpha) have been implicated as mediators of septic shock, with circulating leucocytes being considered a major source for their release. However, plasma cytokine levels of leucocytopenic patients with evolving sepsis have not been studied. We have prospectively measured plasma cytokines during chemotherapy-induced leucocytopenia (< 1 x 10(9)/l) in 50 patients with AML. Cytokine levels in patients with severe sepsis (n = 5) or septic shock (n = 8) were compared to those measured in 13 matched patients with uncomplicated febrile infections. In evolving septic shock, IL-6, IL-8 and TNF-alpha peaked within 48 h of fever onset at levels reported for non-leucocytopenic patients and distinctively higher than during uncomplicated febrile episodes (P < 0.05). Peak concentrations measured within 48 h after onset of fever were related to fatal outcome. IL-1 beta was detected in less than 5% of all samples. Cytokine concentrations were unrelated to leucocyte counts and markers of neutrophil or monocyte activation (elastase and neopterin levels, respectively). We conclude that cytokine release associated with evolving septic shock in patients with AML does not depend on circulating leucocytes.
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PMID:Cytokine response to infection in patients with acute myelogenous leukaemia following intensive chemotherapy. 780 78

Major trauma and consecutively associated infectious complications have a major impact on the mechanisms of the specific immune response and the nonspecific inflammatory reaction. The trauma-induced host defense abnormalities become strikingly evident with the analysis of cytokine synthesis patterns. The dissociation of cell-mediated immune responses following trauma is based upon an overrepresentation of suppressor-active monocytes and inadequate T-cell help in parallel. Corresponding dysregulation of cytokine production appears within many facets. Complement, endotoxin and antigen antibody complexes cause a massive activation of monocytes with an abnormal release of essential mediators, like PGE2, IL-1, IL-6, IL-8, TGF-beta and TNF-alpha. The regulation of cytokine synthesis under stressful conditions is differentially regulated for the individual mediators, either on a transcriptional or a posttranscriptional level. In our opinion, the endogenous provisions of the organism for survival following major injury are inadequate and from this hypothesis we derive the necessity for a substantial exogenous therapeutic intervention. The primary target of modern immunotherapy must be to inhibit the conversion of a systemic inflammatory reaction in immunocompromised patients towards a status of bacterial sepsis. Different approaches appear to be feasible to avoid the development of late multiorgan failure. These interventions have to be utilized preventively in a controlled manner as early as possible after trauma has occurred, and they must effectively protect different cell systems (lymphocytes, monocytes, PMNs and endothelial cells).
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PMID:[Immune mechanisms of post-traumatic hyperinflammation and sepsis]. 782 50

We measured serum levels of endotoxin, cytokines, and eicosanoids and investigated their relationship to serum complement levels in patients with sepsis. Serum endotoxin (Et) levels (5.3 +/- 2.4 pg/ml) were within the normal range, but levels of tumor necrosis factor-alpha (TNF-alpha, 114 +/- 104.94 pg/ml), interleukin 6 (IL-6, 86.7 +/- 50.9 pg/ml), interleukin 8 (IL-8, 86.8 +/- 49.7 pg/ml), type-II phospholipase A2 (type II PLA2, 211.3 +/- 193.9 ng/ml), leukotriene B4 (LTB4, 88.7 +/- 27.2 pg/ml), thromboxane B2 (TXB2, 58.7 +/- 50.9 pg/ml) and 6-keto-prostaglandin F1 alpha (PGF1 alpha, 21.0 +/- 11.0 pg/ml) levels were above normal. Levels of C3a (1088.4 +/- 83.8.7 ng/ml) and C4a (1951.5 +/- 1697.8 ng/ml) were also above normal; C3 (66.0 +/- 25.6 mg/dl) and C4 (23.6 +/- 5.3 mg/dl) were within the normal range, and C5a was lower than the detectable limit in all but one of the subjects. Serum TNF-alpha was significantly correlated with C3a (p < 0.001). Serum IL-6 had a significant negative correlation with C3 (p = 0.002) and C4 (p = 0.010). Type II PLA2 was significantly correlated with C3a (p < 0.001). There were no significant correlations between serum Et or IL-8 and serum C3, C4, C3a or C4a. Our findings suggest that increased levels of TNF-alpha, IL-6, and Type II PLA/ in patients with sepsis contribute to activation of the complement system.
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PMID:Blood cytokine and complement levels in patients with sepsis. 793 3

Sepsis is the most important cause of mortality in the Intensive Care Units. At present, sepsis is understood to be the inflammatory response of the host to infection, rather than a direct effect of microbial aggression. From the clinical standpoint, this inflammatory response is known as systemic inflammatory response syndrome (SIRS). Pathophysiologically, SIRS is characterized by the activation of several groups of cell (monocytes/macrophages, PMNs, and endothelial cells) and by the release of inflammatory mediators (cytokines and others). Tumor necrosis factor (TNF) is the first cytokine released by endotoxin action over monocyte/macrophage. TNF secretion, modulated by interferon gamma (IFN gamma) and interleukin 10 (IL-10), is followed by release of other cytokines such as interleukins (IL) (IL-1, IL-6 and IL-8). These mediators are able to act over hemostasis activating the extrinsic pathway through tissue factor expression. The action of the mediators over endothelial cells induces an increase in plasminogen activator inhibitor type 1 (PAI-1) levels with inhibition of fibrinolysis. Both coagulation activation and fibrinolysis blockade result in fibrin deposit in the microvascular system. The complexity of the mechanisms implicated in systemic inflammatory response make a general rule so difficult to establish, because patient response is highly individualized and it is not possible to know which moment of this dynamic process is being analyzed.
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PMID:Inflammatory mediators and their influence on haemostasis. 795 61

Platelet activating factor acetylhydrolase (PAF-AH) activity was measured in patients with sepsis, and its relationships with various cytokines and endotoxin were evaluated. PAF-AH activity was significantly higher (p = 0.0136) in 17 patients who died than 13 patients who survived. PAF-AH activity showed significant correlations with the plasma endotoxin, TNF-alpha, and IL-8 levels. These findings suggest that PAF-AH activity reflects the severity of the pathological condition.
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PMID:Platelet-activating factor (PAF) acetylhydrolase activity, type II phospholipase A2, and cytokine levels in patients with sepsis. 800 78

Interleukin-8 (IL-8), a neutrophil chemoattractant and activating cytokine, has been implicated as a proinflammatory mediator in gram-negative sepsis. In vitro data support the notion of IL-8 as an endothelial adherence inhibitor. To evaluate this issue, we infused six volunteers with reference endotoxin and measured plasma levels of IL-8, neutrophil tumor necrosis factor alpha (TNF-alpha) receptors, TNF-alpha-induced adherence to fibronectin, and neutrophil chemotaxis to IL-8 and other attractants. We found that, at 3 h postinfusion, IL-8 but not TNF-alpha plasma levels were elevated. Neutrophils had shed L-selectin (mean channel fluorescence decrease, 79 +/- 9 to 49 +/- 7; P = 0.0625) and TNF-alpha receptors (decrease in number of receptors per cell, 1,596 +/- 340 to 574 +/- 93; P = 0.004). Cells were chemotactically desensitized to IL-8. TNF-alpha-induced adherence to fibronectin was suppressed from 69% +/- 5% of the phorbol myristate acetate response to 38% +/- 7% (P = 0.0154). These findings support the notion that release of IL-8 into the vascular space may be an in vivo mechanism for suppression of neutrophil accumulation at extravascular sites. L-Selectin loss would reduce the ability of neutrophils to adhere to activated endothelial cells. The specific loss of migratory response to IL-8 would impair neutrophil delivery to areas where IL-8 was the predominant chemoattractant. Loss of TNF-alpha-induced adherence to fibronectin would blunt those responses, including production of oxidants, capacitated by adherence.
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PMID:Alterations of neutrophil responses to tumor necrosis factor alpha and interleukin-8 following human endotoxemia. 811 67


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