UMLS:C0036690 - FACTA Search

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Query: UMLS:C0036690 (sepsis)
59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Cytokines serve to initiate the acute inflammatory response and to integrate nonspecific and specific immunological responses to infections occurring in perioperative patients. Microbial substances induce macrophages to produce pivotal cytokines (TNF-alpha and IL-1 beta). This results in an activation of other cytokine productions including IL-2, IL-3, IL-4, IL-6, chemokines, and IL-10. Also, other host-originated humoral mediators are released from macrophages, neutrophils, platelets, and endothelial cells Various cytokines are also produced by helper-T (Th) cells, and the Th1/Th2 balance is regulated by cytokines and stress hormones. This nonspecific inflammatory response and specific immunological response which are mediated by cytokines are crucial for the host defense against invading pathogens. On the other hand, the blood levels of TNF-alpha, IL-6, IL-8, and MIP-1 alpha were correlated with the severity and mortality in patients with sepsis. Also we found that in patients with inhalation injury the high IL-8 levels in bronchoalveolar lavage fluid on admission predicted the development of respiratory insufficiency. In severe infection, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines cause an autodestructive systemic inflammatory response syndrome (SIRS). This condition is termed "Cytokine Storm" by the author. In cytokine storm, not only proinflamamtory cytokines, but also anti-inflammatory cytokines appear in circulating blood, leading to septic shock, multiple organ dysfunction, and immunosuppression. With further understanding of the roles of cytokines in sepsis, modulation of cytokine responses could be a new modality of the treatment.
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PMID:[Cytokine-mediated biological response to severe infections in surgical patients]. 903 81

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

Cytokine levels during infection and sepsis have been extensively studied in the past. In contrast to the excellent data on tumour necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and polymorphonuclear (PMN) granulocyte elastase (PMN-E) concentrations in blood, little is known about cytokine and PMN-E levels in tissue or local fluids like abdominal exudate in secondary, purulent peritonitis of man. Therefore, the authors studied perioperative intra-abdominal levels of TNF-alpha, IL-8 and PMN-E in 21 patients with severe purulent peritonitis. The average pre-operative levels of TNF-alpha were 694 +/- 239 pg/ml in exudate and 26 +/- 6 pg/ml in plasma, for IL-8 100 +/- 34 ng/ml and 0.7 +/- 0.5 ng/ml, and for PMN-E 68 +/- 14 microg/ml and 0.7 +/- 0.1 microg/ml, respectively. Standard surgical procedures reduced the intra-abdominal concentrations of cytokines and PMN-E to as low as one tenth of the pre-operative levels. Postoperatively, TNF-alpha and IL-8 levels recovered rapidly and pre-operative levels of IL-8 were reached again after 1 h and for TNF-alpha after 8 h. PMN-E concentration remained below the initial baseline within 8 h of observation. TNF-alpha concentration, but not IL-8 or PMN-E, depended on the microbiological load of the abdominal exudate (< or > 10(3) cfu/ml). There were no significant differences in the intra-abdominal or plasma levels of cytokines or PMN-E between survivors and non-survivors at any observation time.
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PMID:Perioperative pattern of peritoneal interleukin 8, tumour necrosis factor-alpha, and granulocyte elastase release in human secondary peritonitis. 911 38

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.
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PMID:TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. 912 3

The accumulation of sCD14 shed from human monocytes in vivo might correlate with other inflammatory parameters and could be of importance in overcoming a sepsis situation. The development of the sCD14 titer in the supernatant of monocyte-enriched MNC cultures isolated from healthy volunteers was studied utilizing a commercially available sCD14 ELISA. These culture experiments revealed the prolonged liberation of sCD14 into the supernatant during a period of several days. A medium-exchange schedule of 2-3 days was found to be superior to a longer incubation period with respect to the sCD14 yield. PMA initially enhanced the CD14 shedding slightly, but after a few hours it strongly repressed the process. Such a reduction was also achieved by protein synthesis inhibitors (cycloheximide, actinomycin D). Additionally, we monitored the concentration of sCD14, CRP, IL-6 and IL-8 in human sera from healthy persons or patients suffering from severe burn injuries with or without sepsis. Our results indicate that sCD14 is strongly correlated with IL-6, but not with IL-8. sCD14 titers were higher in the group of patients with both burn injuries and sepsis. From experiments with monocyte-enriched MNC cultures isolated from healthy volunteers and medium supplemented with sera containing sCD14 as well as radiolabeled LPS, we conclude that the enhanced shedding of CD14 in vivo during sepsis is probably not able to reduce the binding of LPS to monocytes.
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PMID:Characteristics of CD14 shedding from human monocytes. Evidence for the competition of soluble CD14 (sCD14) with CD14 receptors for lipopolysaccharide (LPS) binding. 926 97

Interfering with the endotoxin-mediated cytokine cascade is thought to be a promising approach to prevent septic complications in gram-negative infections. The synthetic lipid A analog SDZ MRL 953 has been shown to be protective against endotoxic shock and bacterial infection in preclinical in vivo models. As part of a trial of unspecific immunostimulation in cancer patients, we conducted a double-blind, randomized, vehicle-controlled phase I trial of SDZ MRL 953 to investigate, first, its biologic effects and safety of administration in humans and, second, its influence on reactions to a subsequent challenge of endotoxin (Salmonella abortus equi). Twenty patients were treated intravenously with escalating doses of SDZ MRL 953 or vehicle control, followed by an intravenous application of endotoxin (2 ng/kg of body weight [BW]). Administration of SDZ MRL 953 was safe and well-tolerated. SDZ MRL 953 itself increased granulocyte counts and serum levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but not of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. Compared with vehicle control, pretreatment with SDZ MRL 953 markedly reduced the release of TNF-alpha, IL-1beta, IL-8, IL-6, and G-CSF, but augmented the increase in granulocyte counts to endotoxin. Induction of tolerance to the endotoxin-mediated cascade of proinflammatory cytokines by pretreatment with SDZ MRL 953 in patients at risk may help to prevent complications of gram-negative sepsis.
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PMID:Downregulation of the proinflammatory cytokine response to endotoxin by pretreatment with the nontoxic lipid A analog SDZ MRL 953 in cancer patients. 926 88

Human alveolar macrophages (AMs) obtained from smokers and non-smokers by bronchoalveolar lavage (BAL) were subjected to various concentrations of NO2 in an inverted monolayer exposure model. Culture supernatants were collected 4 h after the exposure and assayed for secreted TNF-alpha, IL-1 beta, IL-8 and MIP-1 alpha. The steady state levels of the mRNAs for these cytokines were also analysed in the cells. The adherence of BAL cells to plastic prior to exposure to the gas elevated the steady state mRNA levels of all four cytokines tested in smoker's cells and that of TNF-alpha and IL-1 beta, but not IL-8 (MIP-1 alpha not tested), in non-smoker's cells. Interestingly, adherent cells from non-smokers released circa 15-, 3-, 1.5- and 3-fold the amounts of IL-1 beta, IL-8, TNF-alpha and MIP-1 alpha, respectively, than smoker's cells during control incubation or exposure to air. A 20 min exposure to NO2 (5 or 20 p.p.m.) did not increase the secretion of any of the cytokines from either cell type. In contrast, NO2 caused a concentration-dependent inhibition of the secretion of all cytokines except IL-1 beta from smoker's cells. Additionally, NO2 greatly diminished the release of all cytokines in response to further treatment with lipopolysaccharide (LPS). In contrast, only the secretion of TNF-alpha from non-smoker's cells was inhibited by the gas in a concentration-dependent manner, whilst LPS-induced secretion of the cytokines was not affected by the gas. The steady state levels of the respective mRNAs for each of the cytokines were not significantly affected in smoker's cells by exposure to NO2, except for a negative, dose-dependent trend in the case of TNF-alpha. Nitrogen dioxide also failed to elevate the levels of the mRNAs in non-smoker's cells but, again, tended to diminish the levels, particularly of IL-1 beta mRNA. However, exposure to the gas inhibited LPS-induced accumulation of cytokine mRNAs in smoker's cells only. The data suggest that macrophage-derived cytokine mediators of the sepsis response may not play a role in the generation of NO2-induced inflammation in the human lung. Conversely, the gas seems to non-specifically inhibit the release and/or production of cytokines, particularly from smoker's cells, at the post-transcriptional level, and impairs the ability of the cells to increase the transcription and release of the cytokines in response to bacterial LPS. The fact that NO2 seriously impaired the already diminished capacity of smoker's cells to release several important pro-inflammatory cytokines, both under control conditions and in response to LPS, strongly suggest that the inhalation of NO2 in cigarette smoke may contribute to impairing host defence against infection in the lung.
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PMID:Differential inhibition of inflammatory cytokine release from cultured alveolar macrophages from smokers and non-smokers by NO2. 936 75

Chemokines contribute to the inflammatory response by selective attraction of various leukocytic cell types. Human GCP-2 was originally identified by amino acid sequence analysis as a CXC chemokine co-produced with IL-8 by osteosarcoma cells. Furthermore, the complete coding domain of human GCP-2 was disclosed by means of RT-PCR. Similarly, mouse GCP-2 was isolated from fibroblastoid and epithelial cells and completely identified by sequence analysis. Human and mouse GCP-2 share 61% identical amino acids. Both chemokines occur as multiple NH2-terminally truncated forms. The shorter forms of mouse, but not those of human, GCP-2 showed a higher neutrophil chemotactic potency and gelatinase B releasing capacity. Mouse GCP-2 was a more potent neutrophil activator than human GCP-2, natural mouse KC, and MIP-2. Human GCP-2 was not chemotactic for monocytes, lymphocytes, or eosinophils. Quantitative studies of mRNA expression in diploid fibroblasts revealed GCP-2 induction by IL-1beta. Human GCP-2 induced [Ca2+]i increase in neutrophils, which was reciprocally desensitized by IL-8, GROalpha, and ENA-78. Human GCP-2 induced [Ca2+]i increases and chemotactic responses in both CXCR1- and CXCR2-transfected cells. Finally, GCP-2 provoked neutrophil accumulation and plasma extravasation in rabbit skin. In humans, GCP-2 complements the activity of IL-8 as neutrophil chemoattractant and activator but it constitutes a major neutrophil chemokine in the mouse. GCP-2 induces neutrophil chemotaxis and activation but it might also contribute to detrimental tissue damage in sepsis, acute respiratory distress syndrome, acute hypersensitivity reactions, and autoimmune diseases. It might also influence the invasive capacity of GCP-2-secreting tumor cells.
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PMID:Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage. 936 9

The evidence from animal sepsis models that hemofiltration may ameliorate the hemodynamic changes that occur in septic shock has led to speculation that continuous renal replacement therapy may have nonrenal benefits in septic patients. Much of the subsequent work has been done to elucidate the mechanisms of this benefit, in particular the role of removal of inflammatory mediators including cytokines and complement. The significance of extracorporeal removal of such products is dependent on the relative importance of endogenous production and clearance in the setting of sepsis and multiple organ failure and on the method of blood purification. This article reviews the evidence thus far, consisting of in vitro, animal, and human studies; a range of mediators (TNFalpha, IL-1beta, IL-6, IL-8, complement factors C3a, C5a, and D); various membranes (polyacrylonitrile, polysulfone, and polyamide); and clearance by diffusion, convection, and adsorption. The most consistent results suggest that the plasma levels of some mediators are lowered by a combination of membrane adsorption and convection, the clinical significance of which is still uncertain. The review shows the need for further work to unravel the role of CRRT in treating septic patients.
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PMID:Mediator removal with CRRT: complement and cytokines. 937 78

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