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 aim of this study was to determine whether interleukin-10 would alter locally derived and systemic proinflammatory cytokine expression and protect from the lethality of cecal ligation and puncture. Three groups of Sprague-Dawley rats were used. Group 1 underwent cecal manipulation. Groups 2 and 3 underwent cecal ligation and puncture. Group 2 received intraperitoneal saline injections beginning 1 hour after cecal ligation and puncture and every 3 hours thereafter for 24 hours. Group 3 received intraperitoneal interleukin-10 one hour after cecal ligation and puncture and every 3 hours thereafter. Animals were killed at 6 and 24 hours after cecal ligation and puncture or sham operation. Serum tumor necrosis factor-alpha (TNF-alpha) levels were determined by enzyme-linked immunosorbent assay. TNF-alpha messenger RNA expression was determined by reverse transcriptase-polymerase chain reaction using Beta-actin as the internal standard. There was a twofold increase (P <0.001) in TNF-alpha mRNA in the liver at 6 and 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. There was a twofold increase (P <0.05) in TNF-alpha mRNA in the lung observed only at 24 hours after cecal ligation and puncture when compared to rats treated with interleukin-10. Serum levels of TNF-alpha were elevated at 6 hours in control animals, and this effect was abolished by the administration of interleukin-10. There was no difference in mortality rates at 6 hours (0% for all groups); however, at 24 hours 57% (4/7) mortality was observed in group 2 vs. 0% (0/20) in groups 1 and 3. Interleukin-10 given after the onset of cecal ligation and puncture protects against the lethality of intra-abdominal sepsis.
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PMID:Interleukin-10 protects against lethality of intra-abdominal infection and sepsis. 1063 65

Anti-inflammatory substances are released during septic shock that modulate monocyte function. Decreased monocyte responsiveness to bacterial toxins and decreased expression of human-leukocyte-associated antigen-DR (HLA-DR) have been reported during septic shock and critical illness. Impaired antigen presentation has been inferred from these observations but has not been demonstrated. We assessed antigen presentation and costimulatory molecule expression in 12 age-matched control subjects, 10 noninfected critically ill patients (CINS), and 17 critically ill patients with sepsis (CIS). Antigen presentation was assessed by using in vitro lymphocyte 5-bromo-2-deoxyuridine (BrdU) incorporation in response to tetanus toxoid. The expression of HLA-DR and the costimulatory molecules CD28, CD86, and CTLA-4 was assessed by flow cytometry. Serum interleukin-10 (IL-10) was also measured by enzyme-linked immunosorbent assay. Serum IL-10 levels were significantly elevated in CIS patients (91 +/- 38 pg/mL) as compared with levels in control subjects (5 +/- 4 pg/mL)(P < .05). Lymphocyte BrdU incorporation increased by 710% +/- 243% in control subjects but by only 144% +/- 62% in CIS patients and 76% +/- 31% in CINS patients (P < .01 vs control). Monocyte HLA-DR expression, monocyte CD86 expression, and lymphocyte CD28 expression were significantly decreased in CIS patients (P < .01) as compared with control subjects. Conversely, lymphocyte CTLA-4 expression was significantly increased in CIS patients (P < .05 vs control). Monocyte CD86 expression was also significantly decreased in CINS patients as compared with control subjects. These data indicate that antigen presentation is decreased in critically ill patients with sepsis. This appears in part related to decreased expression of HLA-DR and the costimulatory molecules CD86 and CD28. Increased expression of the negative signal receptor CTLA-4 may also impair antigen presentation in patients with sepsis.
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PMID:Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients. 1069 60

Immunoparalysis is an acquired immunodeficiency which may occur in patients after major surgery, burns, polytrauma and sepsis. It is associated with a modified state of monocytes marked by their altered capacity to induce antigen-specific T cell stimulation and to release various cytokines. However, the pathogenesis of immunoparalysis may differ in various patient groups. It can develop in patients after systemic hyperinflammation induced by gastrointestinal translocation of endotoxin (lipopolysaccharide, LPS) or sepsis, as well as in patients without preceding systemic inflammation but primary anti-inflammation, for instance induced by sympathetic activation. To further elucidate the syndrome, we compared endotoxin tolerance as a model of immunoparalysis after systemic hyperinflammation versus interleukin-10 (IL-10) treatment as a model of primarily anti-inflammation-induced immunoparalysis. In vitro priming of peripheral blood mononuclear cells with either LPS or IL-10 for 24 h led to a strongly or moderately diminished LPS-induced tumor necrosis factor-alpha (TNF-alpha) production, compared to unprimed controls, respectively. Furthermore, LPS-induced reduction of TNF-alpha production capacity persisted over the following days whereas IL-10-primed monocytes rapidly recovered. Similarly, in contrast to persistently diminished MHC class II expression in LPS-treated monocytes, IL-10 only transiently downregulated these molecules. Consequently, in contrast to IL-10-primed monocytes, LPS-primed monocytes were greatly impaired in their capacity to induce antigen-specific T cell proliferation and IFN-gamma production. These data indicate that LPS priming provokes a more profound modulation of monocyte function than IL-10 priming, raising the question of possible variations in the clinical course of immunoparalysis, dependent on its pathogenesis.
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PMID:Comparison of monocyte functions after LPS- or IL-10-induced reorientation: importance in clinical immunoparalysis. 1072 96

The cecal ligation and puncture (CLP) model was used to investigate whether failure of neutrophil migration occurs in sepsis and whether it correlates with disease outcome. It was observed that the severity of sepsis correlates with the number of punctures in the cecum: mice with 2 punctures (sublethal [SL]-CLP) developed mild peritonitis (100% survived), whereas mice with 12 punctures (lethal [L]-CLP) developed severe peritonitis and bacteremia that evolved to sepsis (none survived). The production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-10 was higher in L-CLP than in SL-CLP mice. The impairment of neutrophil migration to the peritoneum and to the cecum wall was observed only in L-CLP mice. This phenomenon was shown to be mediated by nitric oxide, because aminoguanidine prevented the failure of neutrophil migration and improved the survival of L-CLP animals. In conclusion, impairment of neutrophil migration is a crucial event in the worsening of sepsis, and nitric oxide seems to be responsible for the phenomenon.
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PMID:Role of nitric oxide in the failure of neutrophil migration in sepsis. 1088

Mast cells participate in the host response during sepsis and have been shown to have a protective effect in a murine model of acute septic peritonitis and multi-organ failure initiated by cecal ligation and puncture (CLP). Stem cell factor (SCF) is a hematopoietic cytokine important in mast cell proliferation and activation. In the present study, we examined the protective effects of a single intraperitoneal injection of SCF given 2 hours before CLP surgery in mice. Four days after the CLP surgery, SCF pretreatment significantly improved mouse survival from 29 to 56% and mast cells were absolutely required for this effect. Immunoneutralization studies revealed that the SCF-stimulated release of monocyte chemoattractant protein-1 (MCP-1) into the septic peritoneal cavity contributed to the protective effect of SCF in this model. One potential cellular source of MCP-1 was the SCF-activated mast cell. In addition, SCF pretreatment significantly augmented circulating levels of SCF and the immunomodulatory cytokine interleukin-10 in septic mice, in part because the SCF pretreatment seemed to promote the release of both mediators from the liver. Additional hepatic effects of SCF treatment included an accelerated expression of hepatic levels of signal transducer and activator of transcription-3 (STAT-3) in CLP mice pretreated with SCF. Taken together, the findings from the present study demonstrate that the intraperitoneal delivery of SCF has a major protective effect in a murine model of CLP.
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PMID:Novel protective effects of stem cell factor in a murine model of acute septic peritonitis. Dependence on MCP-1. 1102 22

Nutritional intervention with omega-3 fatty acids during trauma and infection has been shown to improve the clinical outcome of patients and the survival rate in laboratory animals. This study evaluated the effects of parenteral administration of lipid emulsions containing fish oil (FO) or soybean oil (SBO) on survival and T-lymphocyte response during sepsis. Male Sprague-Dawley rats (250-275 g) were prepared for parenteral feeding 4 d before inducing sepsis by cecal ligation and puncture (CLP). Standard resuscitation was provided with normal saline. Thirty minutes after completing CLP, sham control or CLP rats were infused continuously with saline or a parenteral diet containing SBO or a 1:1 FO:SBO emulsion. The survival rate was significantly improved in rats receiving the FO-supplemented diet, with 50% alive by 120 h in comparison with the saline-infused, chow-fed rats (0% alive by 120 h) or the SBO-fed rats (12% alive at 120 h). The T-lymphocyte response was evaluated at 24 h after CLP. Sepsis led to a decline in lymphocyte proliferation in rats infused with saline or the SBO emulsion, which was associated with a greater release of splenocyte interleukin-10, transforming growth factor-beta and prostaglandin E2. Administering the 1:1 FO:SBO parenteral diet during sepsis improved the survival rate and prevented the sepsis-induced suppression of lymphocyte proliferation and interleukin-2 release. The FO effect on lymphocyte function was associated with decreased splenocyte release of transforming growth factor-beta and prostaglandin E2.
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PMID:Parenteral supplementation with a fish-oil emulsion prolongs survival and improves rat lymphocyte function during sepsis. 1124 Mar 46

The contribution of individual Fcgamma receptor (FcgammaR) subclasses to meningococcal phagocytosis was studied. In addition, functional FcgammaR polymorphisms were determined in 50 patients with meningococcal disease (MD), in 183 first-degree relatives of MD patients, and in 239 healthy control subjects, to study the association of FcgammaR genotypes with disease. Efficient internalization of opsonized Neisseria meningitidis serogroup B was mediated via multiple FcgammaR subclasses on phagocytes. Accordingly, a low-efficiency combination of FcgammaRIIa-R/R131, FcgammaRIIIa-F/F158, and FcgammaRIIIb-NA2/2 genotypes was increased significantly in relatives of patients with MD, compared with healthy control subjects (P<.05; odds ratio, 2.6; 95% confidence interval, 1.1-6.3). FcgammaRIIa and FcgammaRIIIa genotype distributions differed between patients with sepsis and those with meningitis. Combined genotypes of FcgammaRIIa and interleukin-10 -1082, which was previously reported as being associated with MD outcome, were distributed randomly in control subjects but not in relatives of patients with MD (P<.01). These data provide further evidence for the association of polymorphic genes on chromosome 1 and MD.
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PMID:Relevance of Fcgamma receptor and interleukin-10 polymorphisms for meningococcal disease. 1174 Jul 30

Lipopolysaccharides in the outer membrane of Neisseria meningitidis are key molecules that induce inflammation and cause meningitis and shock. Mutant strains, with altered lipid A, the toxic moiety of lipopolysaccharide, or completely lacking lipopolysaccharide, induce significantly less inflammation than wild-type strains. Polymorphism of the Fc gamma receptors and interleukin-10 gene but not of the Toll-like receptor 4 may influence the development of meningococcal infection. Mannan-binding lectin is involved in complement activation, the regulation of adhesion molecules and cytokine production induced by meningococci. The activation of protein C by the thrombomodulin protein C receptor complex on the endothelial cell surface appears to be reduced in meningococcal sepsis but is still sufficient to convert protein C to activated protein C in patients treated with concentrated protein C.
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PMID:Current concepts in the role of the host response in Neisseria meningitidis septic shock. 1201 58

Recent studies have demonstrated gender differences in the immune response following hemorrhagic shock with an enhanced immune function and lower mortality following subsequent sepsis in females. Early interleukin-10 (IL-10) treatment has been shown to have beneficial effects on the depressed immune function in males, but not in females following shock. However, it remains unclear if the observed gender-related effect of IL-10 treatment results in an advantage following subsequent polymicrobial sepsis. To study this, male and female CBA/J mice (age 2-3 months) were subjected to hemorrhage (35 +/- 5 mmHg for 90 min and fluid resuscitation). At resuscitation, each received either 10 microg of recombinant murine IL-10 or placebo i.p.. At 48 h after resuscitation, either peritoneal macrophages (pMphi) and plasma were harvested, or polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Following CLP, either survival over 10 days was measured, or pMphi and plasma were harvested 4 h after CLP to assess TNF-alpha, IL-6, IL-10, and prostaglandin E2 (PGE2) release of pMphi and plasma levels of IL-10, free testosteron, and 17-beta estradiol. Early IL-10 treatment restored depressed proinflammatory immune response in males (TNF-alpha and PGE2), which was associated with an enhanced survival (P < 0.05) following subsequent sepsis as compared with placebo-treated mice (8/20 and 1/20, respectively). In contrast, the immune response and survival in females receiving IL-10 was not significantly changed, although females treated with IL-10 had a trend towards higher mortality (7/15 and 2/15, respectively; P = 0.08). Thus, early IL-10 anti-inflammatory treatment following hemorrhage has potential beneficial effects only in males associated with enhanced survival following subsequent sepsis.
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PMID:Early interleukin-10 treatment improves survival and enhances immune function only in males after hemorrhage and subsequent sepsis. 1209 29

We report a case of toxic shock-like syndrome due to a rare infection of group G Streptococcus bacteremia in a patient with idiopathic thrombocytopenic purpura and its successful treatment with continuous venovenous hemofiltration (CVVH). As the result of sepsis treatment with CVVH, in addition to administration of vasopressors and antibiotics, serum levels of interleukin-1beta, interleukin-10 and tumor necrosis factor-a fell and shock was controlled.
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PMID:Serum cytokine level during continuous venovenous hemofiltration in toxic shock-like syndrome due to group G beta Streptococcus bacteremia in a patient with idiopathic thrombocytopenic purpura. 1216 Jan 64


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