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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that, during sepsis, the balance of pro- and anti-inflammatory cytokines is related to severity and survival. Cecal ligation and puncture (CLP) with a large (18-gauge)-, intermediate (21-gauge)-, or small (26-gauge)-diameter needle, or sham laparotomy, was performed on outbred CD-1 mice. Concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 were measured (by enzyme-linked immunosorbent assay) in serum, peritoneal lavage fluid, and liver and lung samples at 4, 8, 24, 48, and 96 h. As the diameter of the CLP needle decreased, the mortality rate decreased (at 48 h: large, 80%; intermediate, 40%; small, 20%; P < 0.05), the TNF-alpha and IL-6 concentrations decreased, and the time-to-peak TNF-alpha expression increased. In contrast, IL-10 concentration increased compared with baseline (serum at 24 h: large, 2.3-fold +/- 1.6-fold; intermediate, 2.0-fold +/- 0.5-fold; small, 49.9-fold +/- 8.3-fold; P < 0.05). Administration of IL-10 (5 microg, intraperitoneal) prior to CLP decreased mortality (P < 0.001). Administration of polyclonal anti-IL-10 serum prior to CLP (0.5 ml intraperitoneal) had the opposite effect and increased mortality (P < 0.001) and TNF-alpha, IL-6, and TNF-alpha mRNA expression compared with controls. Thus, severe sepsis is associated with a largely unopposed inflammatory response, and a largely unopposed inflammatory response (with anti-IL-10) results in severe sepsis and death. Less severe sepsis is associated with greater anti-inflammatory mediator expression, and greater anti-inflammatory mediator expression (with IL-10) results in less severe sepsis. Thus, the balance of inflammatory mediators is related to the severity and mortality of murine sepsis.
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PMID:Balance of inflammatory cytokines related to severity and mortality of murine sepsis. 889 Feb 33

Cytokines play a major role in the pathophysiology of sepsis and septic shock. Using enzyme immunoassays the acute serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and leukemia inhibitory factor (LIF) were investigated in 90 patients with positive blood cultures and clinical signs of infection. In 27 patients samples were obtained on admission, after 1, 4, 12, 18, and 24 h, and then daily. The acute serum levels of IL-6, TNF-alpha, G-CSF, and IL-8 were significantly higher among patients with severe sepsis. Patients with Gram-negative infection had significantly higher levels of TNF-alpha on admission than did patients with Gram-positive infections (p = 0.0008). The levels of IL-6, G-CSF and, to some extent, TNF-alpha decreased rapidly in survivors within the first 24 h of admission to hospital and institution of treatment. LIF was detected in 8/90 in both survivors and nonsurvivors.
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PMID:Dynamics of blood cytokine concentrations in patients with bacteremic infections. 889 5

This study reports the predictive value, in septic patients, of septic shock at presentation (SS factor) alone and in combination with multiple markers, using survival of the sepsis episode as the outcome measure. The SS factor correctly predicted the outcome in 53/68 (78%) of patients in this study. The Acute Physiology and Chronic Health Evaluation II Score (APACHE II or APII) and interleukin-6 (IL-6) and IL-6 soluble receptor (IL-6sR) concentrations were evaluated in combination with the SS factor in the same 68 patient population which was randomly divided into design (# = 50) and test groups (# = 18). Two iterations of an algorithm were evaluated using randomized patient groups corresponding to those producing the best (Group A) and worst (Group B) performance using a neural network. The four-input algorithm (APII, IL-6, IL-6sR, SS factor) correctly classified 16/18 (89%, Group A) and 14/18 (78%, Group B) of patients in the test subset. The corresponding four-input neural network model (10 iterations) correctly classified 61 to 89% of the 18 patients in the 10 test subsets.
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PMID:Multiparameter models for the prediction of sepsis outcome. 890 16

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.
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PMID:Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia. 893 27

Different immunologic parameters were measured in cord blood to test their usefulness in the early diagnosis of early onset sepsis. Cord blood levels of circulating intercellular adhesion molecule-1 (cICAM-1), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly elevated in septic compared to nonseptic neonates. No significant difference between either population was seen for cord blood C3a and elastase-alpha 1-proteinase inhibitor complex (E alpha 1 PI). Measured concentrations of cICAM-1, IL-6 and IL-8 in fetal and maternal blood did not correlate, indicating that the neonate's response to sepsis is clearly different from the mother. Our data suggest that cord blood measurements of cICAM-1, IL-6 and IL-8 might be useful in identifying neonates with early-onset sepsis.
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PMID:Immunologic parameters in cord blood indicating early-onset sepsis. 896 10

The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.
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PMID:Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis. 901 Jun 79

We evaluated the protective effect of fosfomycin (FOM) and an enantiomer of fosfomycin [FOM (+); an isomer of FOM with no bactericidal activity] on murine gut-derived sepsis caused by Pseudomonas aeruginosa. Endogenous bacteremia was induced by administering cyclophosphamide (CY) and ampicillin to specific-pathogen-free mice fed P. aeruginosa. Treatment of mice with FOM at 250 mg/kg of body weight per day twice a day after the second CY administration significantly increased the survival rate compared to that for control mice treated with saline. Treatment with FOM (+) at 20 and 100 mg/kg also significantly increased the survival rate (from 30% for control mice to 80% for treated mice). The bacterial counts in the liver and blood were both significantly lower in FOM(+)-treated mice in comparison with those in liver and blood of saline-treated control mice. FOM(+) administration affected neither the bacterial colonization in the intestinal tract nor the leukocyte counts in the peripheral blood of the mice. After intravascular inoculation of P. aeruginosa, treatment of mice with FOM (+) did not enhance bacterial clearance from the blood of mice pretreated or not enhance bacterial clearance from the blood of mice pretreated or not pretreated with CY, FOM(+) significantly suppressed tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 levels in the serum of mice after gut-derived sepsis. These results indicate that both FOM and FOM(+) have protective effects against P. aeruginosa bacteremia, despite a lack of specific activity of FOM(+), and suggest that FOM may possess immunomodulating activity and that it induces a protective effect. The protective mechanism is speculated to be that FOM modulates the vivo production of inflammatory cytokines.
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PMID:Immunomodulating effect of fosfomycin on gut-derived sepsis caused by Pseudomonas aeruginosa in mice. 902 Nov 84

A review on the possible involvement of tumor necrosis factor-alpha (TNF) in cachexia is presented. While this cytokine is definitely linked to sepsis and tumor-associated weight loss in some experimental models, other cytokines, such as interleukin-6 (IL-6) or interferon-gamma (IFN-gamma), alone or in combination with TNF, may also play an important role in the development of cachexia.
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PMID:Is TNF really involved in cachexia? 902 89

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

Serum levels of hepatocyte growth factor (HGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were determined at the time of admission in 38 patients with acute pancreatitis. The clinical utility of HGF for the detection of severe pancreatitis and for predicting prognosis, bacterial infection (infected pancreatic necrosis or sepsis), and organ dysfunction (liver, kidney, and lung) during the clinical course of acute pancreatitis was compared with the clinical utility of CRP and IL-6 by analysis of receiver operator characteristic (ROC) curves. The optimum cutoff levels of HGF for severity, prognosis, infection, hepatic dysfunction, renal dysfunction, and respiratory dysfunction were 0.9, 1.1, 1.0, 1.1, 1.1, and 1.0 ng/ml, respectively. HGF was as useful as CRP and more useful than IL-6 for detection of severe pancreatitis and for predicting hepatic dysfunction. Moreover, HGF was more useful than CRP or IL-6 for predicting prognosis, renal dysfunction, and respiratory dysfunction. However, for predicting infection, CRP was more useful than HGF. These results suggest that serum HGF levels on admission may be a useful new clinical parameter for determining the prognosis of acute pancreatitis and that HGF may be closely related to the organ dysfunction of acute pancreatitis.
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PMID:Hepatocyte growth factor in assessment of acute pancreatitis: comparison with C-reactive protein and interleukin-6. 905 97


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