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)

Patients suffering from serious bacterial infection present to the hospital after early inflammatory events, such as release of tumor necrosis factor (TNF), have been initiated. The role of other cytokines, such as interleukin-8 (IL-8), a neutrophil chemoattractant and activator, in the pathophysiology of human sepsis is not well characterized, and there are only limited data on IL-6. We studied serial concentrations of TNF, IL-6 (involved in the acute-phase response), and IL-8 in plasma and leukocyte levels of mRNA for these cytokines in patients with localized and septicemic Pseudomonas pseudomallei infection on admission to the hospital and during a prolonged recovery phase (up to 30 days). Of 18 patients, 8 had detectable plasma IL-8 and all had raised plasma IL-6 concentrations. In patients who died median initial concentration of IL-8 (167 pg/ml; range, 97 to 362 pg/ml) and IL-6 (4,800 pg/ml; range, 60 to 9,245 pg/ml) in plasma were higher than those in survivors (P less than 0.008 and P = 0.007, respectively). Septic patients who survived and patients with localized disease had similar cytokine levels. Plasma IL-8 and IL-6 concentrations were elevated throughout the inpatient period of recovery. Circulating leukocytes contained mRNA for IL-8 but not for IL-6 and TNF, and they may secrete IL-8. An elevated plasma IL-6 concentration (greater than 1,000 pg/ml) had 75% mortality) was the best predictor of mortality in P. pseudomallei sepsis. Fifty percent of patients with detectable plasma IL-8 concentrations died. In contrast, plasma TNF bioactivity did not relate to outcome; 75% of patients who did never had detectable plasma TNF activity.
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PMID:Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma and of leukocyte interleukin-8 mRNA levels during septicemic and localized Pseudomonas pseudomallei infection. 137 98

The effects of glutamine concentration on the phagocytosis of an opsonized antigen, the synthesis of RNA, and the production of interleukin-1 (IL-1) by macrophages were investigated in vitro. A minimum A minimum of 0.125 mmol/L glutamine was required for a significant increase in phagocytosis of opsonized sheep erythrocytes, compared with that recorded for macrophages cultured in the absence of glutamine. The synthesis of 3H-RNA by macrophages also required 0.125 mmol/L glutamine in the culture medium before it was significantly increased above the levels of control cultures. A minimum of 0.03 mmol/L glutamine was required for the induction of significant levels of IL-1 by lipopolysaccharide (LPS)-stimulated macrophages. Therefore, recent findings suggesting that decreases in plasma glutamine resulting from major burn injury, sepsis, trauma, and surgery may be partly responsible for the associated impairment of immune function now have a basis in both phagocytosis and in modulation of the synthesis of IL-1 (the first cytokine of the interleukin cascade that leads to specific immunity) by macrophages, in addition to the previously established dependency of lymphocytes on external sources of glutamine for their replication.
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PMID:Glutamine and macrophage function. 138 59

Interleukin-8 (IL-8) is a chemotactic and activating cytokine for neutrophils, which plays an important role in acute inflammatory responses. We aimed to develop a sensitive enzyme-linked immunosorbent assay (ELISA) for IL-8 and established 18 clones of anti-IL-8 monoclonal antibodies (mAbs). These mAbs were evaluated in terms of their antigen-binding affinities, and five clones were selected and used for the comparative study of various combinations of antibodies in sandwich ELISA. Affinity purified rabbit polyclonal antibody was also used in this study. One antibody pair, which showed relatively high sensitivity and which was not severely interfered with blood components, was selected and the assay conditions were optimized by choosing the appropriate buffer for sample dilution and by directly labeling the second antibody with enzyme. The finalized ELISA, using polyclonal antibody as first (coated) antibody and horseradish peroxidase-labeled mAb (clone EL139) Fab' fragment as second antibody, could detect as low as 2.5 pg/ml (0.125 pg/well) of IL-8 by in total 2 h incubation, without being affected by body fluid components. The ELISA was specific to IL-8, showing no cross-reactivity with other cytokines or various IL-8 family proteins which share some amino acid sequence homology with IL-8. As an example of its application to clinical specimens, plasma samples from patients with septic shock were measured. The results showed that sepsis patients contain significantly higher levels of plasma IL-8 compared to normal controls. When analyzed by gel-filtration chromatography, IL-8 in sepsis plasma was eluted in a molecular weight (M(r) region corresponding to the monomer form. The ELISA established here is expected to be effectively used for further investigations on the relationship between IL-8 and various diseases.
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PMID:A highly sensitive enzyme-linked immunosorbent assay for the measurement of interleukin-8 in biological fluids. 138 37

Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a variety of cell types primarily in association with disease states or during host perturbation such as immune responses. At pM or even fM concentrations, IL-1 triggers various responses in nearly all cells. It appears that there is little or no major role for IL-1 in homoeostatic mechanisms. There are two IL-1's (alpha and beta) each with its distinct sequence; there are two IL-1 receptors. Disease states such as local and systemic infection, septic shock, degenerative arthritis and autoimmune diseases such as nephritis, vasculitis and inflammatory bowel disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak and death occur in animals after a combination of tumour necrosis factor (TNF) and IL-1 which is more effective in inducing these changes than either cytokine alone. IL-1 is also a potent inducer of endothelial cell adhesion molecules, IL-6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for reducing the effects of IL-1 have been based on suppression of transcription, translation, or secretion; more recently, receptor blockade has been a new approach. A naturally occurring IL-1-specific receptor antagonist (IL-1ra), which shares 40% conserved amino-acid homology with IL-1 beta, binds to IL-1 surface receptors with the same affinity as IL-1 but does not possess agonist activity and acts as a competitive inhibitor of IL-1. Studies using the IL-1ra to block endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a key role in triggering the cascade of inflammatory responses. In addition, the IL-1ra reduces the spontaneous production of growth factors and proliferation of leukaemic cells. The IL-1ra may be an advantageous therapy in patients with sepsis, diabetes, inflammatory bowel, arthritis and cancer.
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PMID:Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism. 139 23

Cytokines are immunoregulatory molecules that are important mediators of the host response to stress and infection. Infants and children undergoing major surgery are particularly at risk of developing sepsis and have altered metabolic responses to surgical stress compared to adults. We have investigated the temporal sequence of cytokine responses in six infants (mean age, 11 +/- 7.5 months) undergoing pull-through operation for Hirschsprung's disease and correlated them with hemodynamic and biochemical parameters. Tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA preoperatively, intraoperatively (hourly), and 24 and 48 hours postoperatively. IL-6 levels increased significantly in all cases within 2 hours of commencement of the operation (P less than .01) and were maximal 24 hours postoperatively. No significant changes in IL-1 beta levels (mean range, 70 to 110 pg/mL) were seen in these patients. TNF levels were undetectable (less than 20 pg/mL) throughout the study. Cortisol levels were increased in all patients during operation. Serum C-reactive protein levels were first detected 24 hours postoperatively and continued to increase 48 hours postoperatively. Hemodynamically, heart rate increased during the first 3 hours of operation and correlated with increase in IL-6 levels. Blood pressure and temperature changes did not correlate with cytokine levels. This study identifies IL-6 as the earliest detectable cytokine response associated with major surgery in infants. It also suggests that IL-6 can be unregulated, independently of other cytokines, in response to surgical stress.
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PMID:Early induction of IL-6 in infants undergoing major abdominal surgery. 140 30

Group B streptococci (GBS) are a leading cause of sepsis and meningitis in neonates. Since cytokines are thought to play an important role in septic shock, we have studied serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in BALB/c mice infected with type III GBS. TNF alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial serum samples obtained after infection. After i.p. challenge with an LD50, serum TNF alpha rose above baseline values as early as 3 hr, peaked at 7 hr, and returned to baseline values at 20 hr. IL-6 serum levels rose concomitantly with TNF alpha, peaking 8 hr after challenge. No serum TNF alpha activity was detected in the course of sublethal infections. However, a transient rise in TNF alpha levels was observed after i.v. inoculation of high numbers (greater than or equal to 1 x 10(8) of heat-killed GBS. When groups of mice were injected i.v. with a single dose of anti-TNF alpha rabbit serum 2 hr before challenge with an LD90 or LD30, no effect was noted in terms of survival, although the serum TNF alpha peak was completely abrogated. Serum TNF alpha does not seem to play an obligatory role in GBS-induced lethality of adult mice. However, further studies are needed to assess better the role of this cytokine in the pathogenesis of GBS sepsis.
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PMID:Production of tumor necrosis factor-alpha and interleukin-6 in mice infected with group B streptococci. 142 22

It has been demonstrated that the initiation of extracorporeal membrane oxygenation (ECMO) is associated with an increase in the circulating plasma levels of inflammatory mediators. We have expanded the study of these substances to include measurements of complement activation, prostaglandin production, endotoxin appearance, oxygen-derived free radical generation, and cytokine release before, during, and after ECMO. A reproducible second phase of complement activity and prostaglandin synthesis was associated with the appearance of detectable circulating endotoxin (0.04 U/mL pre-ECMO to 0.07 U/mL at 36 hours, P less than .05). Oxygen-derived free radical activity also increased (2 ng/mL to 3 ng/mL at 36 hours, P less than .05), as did plasma levels of tumor necrosis factor (40 pg/mL to 70 pg/mL at 36 hours, nonsurvivor group: P less than .05). Interleukin-1 was elevated above normal, but there were no significant variations noted during the time period studied. Small amounts of interleukin-6 were also detected in the occasional patient. None of these mediators differed significantly between survivors and nonsurvivors. These data indicate that ECMO is associated with a previously undescribed, endotoxin-related, generalized inflammatory state after 36 hours of support. The pulmonary, renal, and cardiac dysfunctions documented with prolonged bypass can all be related to a classic sepsis syndrome.
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PMID:Elevated levels of endotoxin, oxygen-derived free radicals, and cytokines during extracorporeal membrane oxygenation. 143 29

Interleukin-1 alpha (IL-1 alpha) produced alterations in human dermal fibroblast glucose metabolism in vitro of the type seen in severe sepsis in man. Glycolysis and glucose uptake were increased but the oxidation of glucose within the tricarboxylic acid (TCA) cycle was reduced. The combined addition of tumour necrosis factor alpha (TNF alpha) with interferon-gamma (IFN-gamma) similarly increased the dependency for cellular energy provision from an oxidative to the glycolytic state. These cytokine-induced changes in glucose metabolism were unaffected when prostaglandin production was inhibited with a cyclo-oxygenase inhibitor, but were significantly reduced by the steroid dexamethasone. Thus, the inflammatory cytokines IL-1 and TNF alpha reportedly detected in the circulation during severe sepsis may directly affect not only glucose uptake but also its subsequent metabolism within tissue fibroblasts.
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PMID:Inflammatory cytokines stimulate glucose uptake and glycolysis but reduce glucose oxidation in human dermal fibroblasts in vitro. 151

Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung.
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PMID:Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages. 152 Apr 90

There is increasing experimental and clinical evidence that a number of cytokines play a major role in the response to injury and infection and in the development of organ damage in critically ill patients. Tumour necrosis factor (TNF) is now proposed to be a key mediator of organ injury during sepsis. It is elevated early in the course of septic shock and high levels correlate with unfavourable outcome. In animals it can produce the effects of endotoxin. The prophylactic administration of anti-TNF antisera protects mice and rabbits from lethal effects of lipopolysaccharide. Interleukin-1 (IL-1) is an endogenous pyrogen which induces leukocytosis and muscle catabolism. It causes hypotension and tachycardia by reducing smooth muscle contractility. IL-1 receptor blockers have been shown to diminish mortality in experimental endotoxic shock. Interleukin-6 (IL-6) is a pyrogen and lymphocyte activator. It is the major stimulus to acute phase protein production by the liver. A recently described neutrophil-activating peptide (Interleukin-8; IL-8) may be involved in the pathogenesis of ARDS. High blood levels of IL-8 have been found in patients with septic shock. Platelet-derived growth factor (PDGF) has been shown to stimulate TNF production, leukocyte chemotaxis and pulmonary vasoconstriction in response to endotoxin. Other cytokines and growth factors have not yet been studied in critical illness. The cytokine network can be either protective or damaging. Its activation during critical illness triggers complex and still poorly understood interactions. A better comprehension of its role in protection from infection and in the pathogenesis of multiple organ failure may allow therapeutic manipulations aimed at minimising adverse effects while retaining immunological protection.
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PMID:The cytokine network in the critically ill. 152 67


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