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)

Production of oxygen radicals is required for both microbicidal and tissue-toxic effector functions of granulocytes. Inasmuch as an ambivalent role of polymorphonuclear leukocytes (PMNs) may become apparent during sepsis, we studied levels of hydrogen peroxide (H2O2) production by PMNs depending upon the nature of different particulate and soluble stimuli in patients with increasing sepsis severity. Patients with sepsis (n = 15), severe sepsis (n = 12), or septic shock (n = 33) were prospectively enrolled in the study. Healthy volunteers of comparable age and sex served as controls (n = 50). Unopsonized and opsonized zymosan particles were used to assess adhesion, phagocytosis, and the associated H2O2 production. Zymosan particles are rich in beta-glucans and lectin structures that are known to trigger H2O2 production via two major non-toll-like receptor pathogen recognition receptors, comprising the lectin-binding site in the alpha-chain (CD11b) of the complement receptor type 3 and the more recently identified nonclassical C-type lectin, dectin-1. To determine H2O2 production upon cell activation by soluble stimuli, PMNs were activated by the chemotactic tripeptide (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) alone or after priming of cells by preincubation with tumor necrosis factor alpha. To get insight into the changes of fMLP receptor classical intracellular signaling pathways, PMNs were also incubated with the calcium ionophore A23187 and the phorbol ester phorbol myristate acetate, bypassing receptor-dependent signal transduction to directly activate calcium/calmodulin kinase- and protein kinase C-dependent pathways, respectively. As compared with healthy volunteers, levels of H2O2 production by PMNs from septic patients varied depending upon the nature of the activating signal: reduced (zymosan), unchanged (phorbol myristate acetate, opsonized zymosan), and enhanced (spontaneous, fMLP, fMLP + tumor necrosis factor alpha, A23187), with the changes most pronounced in patients with septic shock. Specifically, phagocytosis of zymosan and the associated H2O2 production were significantly decreased whereas spontaneous and stimulated H2O2 production elicited by soluble stimuli strongly increased. Thus, these findings suggest the development of a PMN dysfunction syndrome in patients with increasing sepsis severity. Moreover, as binding of zymosan particles to the PMNs' surface remained unchanged despite increasingly suppressed phagocytosis and associated H2O2 production, observed effects are likely to reflect defects in signaling by the lectin-binding site of CD11b and/or the beta-glucan receptor dectin-1, respectively.
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PMID:Polymorphonuclear leukocyte dysfunction syndrome in patients with increasing sepsis severity. 1691 50

Septicemia is an emerging pathological condition involving, among other effects, refractory hypotension and heart dysfunction. Here we have investigated the contribution of resident nonmyocytic cells to heart alterations after lipopolysaccharide administration. These cells contributed to the rapid infiltration of additional inflammatory cells that enhance the onset of heart disease through the release of inflammatory mediators. Early activation of resident monocytic cells played a relevant role on the infiltration process, mainly of major histocompatibility complex class II- and CD11b-positive cells. This infiltration was significantly impaired in animals lacking the nitric-oxide synthase-2 (NOS-2) gene or after pharmacological in-hibition of NOS-2 or cylooxygenase-2, suggesting a significant contribution of nitric oxide and prostanoids to the infiltration process. Under these conditions, the expression of NOS-2 and cylooxygenase-2 in the whole organ was attenuated because cardiomyocytes failed to express these enzymes. However, cardiomyocytes expressed and activated matrix metalloproteinase-9 through mechanisms regulated, at least in part, by nitric oxide and prostaglandins in an additive way. These results directly link the inflammatory response in the heart and extracellular matrix remodeling by the matrix metalloproteinases released by the cardiomyocytes, suggesting that activation and recruitment of inflammatory cells to the heart is a major early event in cardiac dysfunction promoted by septicemia.
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PMID:Infiltration of inflammatory cells plays an important role in matrix metalloproteinase expression and activation in the heart during sepsis. 1707 81

This study investigated the effect of n-3 fatty acids on adhesion molecules and tissue myeloperoxidase (MPO) activity in diabetic mice with sepsis. Diabetes was induced by a streptozotocin injection. Mice with blood glucose levels exceeding 2000 mg/l were considered diabetic. Diabetic mice were assigned to two groups with a medium-fat (10 %, w/w) diet either provided by soyabean oil (SO, n 30) or fish oil (FO, n 30). n-3 fatty acids provided 4.3 % of the total energy and the n-3/n-6 fatty acid ratio was 1:2 in the FO diet. After feeding the respective diet for 3 weeks, all mice had sepsis induced by caecal ligation and puncture (CLP) and were killed at 0, 6 or 24 h after CLP, with ten mice at each time-point. The result showed that compared with the SO group, FO group had lower PGE2 and TNF-alpha levels in peritoneal lavage fluid after CLP. Lymphocyte CD11a/CD18 expressions were higher at 6 h, whereas the percentage was lower at 24 h in the SO group than in the FO group. Neutrophil CD11b/CD18 expressions were significantly higher in the SO group than in the FO group at 0 h. The FO group had lower organ MPO activities at various time-points after CLP when compared with those of the SO group. The present findings suggest that compared with the diabetic mice fed SO, a low-dose n-3 fatty acid supplementation may attenuate leucocyte adhesion and infiltration into tissues in diabetic mice complicated with sepsis.
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PMID:Effect of dietary fish oil supplementation on cellular adhesion molecule expression and tissue myeloperoxidase activity in diabetic mice with sepsis. 1734 81

Neonatal sepsis occurs from 1 to 21 newborns out of 1 000 live births with mortality rates as high as 30% up to 69%. The most important risk factors are prematurity, low birth weight, invasive medical procedure and prolonged hospitalization in neonatal intensive care units. An aimed and restrictive antibiotic therapy has an outstanding importance to reduce both morbidity-mortality rates and multiple drug-resistance. Generally, preterm newborns present nonspecific clinical signs of infection. The use of high sensitivity infection markers and a negative predictive value (near 100%) are important to distinguish infected and noninfected patients before the culture results and to verify adequacy and duration of antibiotic therapy. This article reviews the immunologic function and practical use of C reactive protein (CRP) and other markers in the diagnosis of neonatal sepsis. While CRP is a specific late infection marker, cytokines, cell surface markers and procalcitonin (PCT) are early infection markers. The use of multiple markers as CRP, PCT, IL-6, IL-8, CD64, CD11b is useful both to early (24-48 h) diagnose of neonatal sepsis, and to monitorate the antibiotic treatment while waiting for the results of cultural examinations.
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PMID:[Evaluation of C reactive protein and others immunologic markers in the diagnosis of neonatal sepsis]. 1751 72

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1(+)CD11b(+) population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1(+) cells effectively suppress antigen-specific CD8(+) T cell interferon (IFN) gamma production but only modestly suppress antigen-specific and nonspecific CD4(+) T cell proliferation. GR-1(+) cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell-dependent and depression of Th1 cell-dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain-containing adaptor-inducing IFN-beta, or the IFN-alpha/beta receptor, is required for complete GR-1(+)CD11b(+) expansion. GR-1(+)CD11b(+) cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization.
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PMID:MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. 1754 19

We have reported that an extract of the edible officinal mushroom Agaricus blazei Murill (AbM) stimulates synthesis of pro-inflammatory cytokines in human monocytes and vein endothelial cells in vitro and reduces the extent of lethal septicemia in mice with bacterial peritonitis. In the present study on human monocytes and granulocytes in whole blood ex vivo, we studied the dynamic changes of cell adhesion molecules (CD11b, CD62L) and the production of reactive oxygen species (ROS) after stimulation with AbM. The presence of AbM resulted in a similarly increased expression of CD11b in monocytes and granulocytes, although at a lower AbM concentration in monocytes (0.5%) than in granulocytes (2%). Furthermore, there was an AbM-mediated decrease in CD62L expression mirroring the effect on CD11b expression regarding magnitude and dose response. The intracellular production of ROS increased slightly but significantly in granulocytes, but not in monocytes stimulated with AbM. The results suggested that the major effect of AbM on monocytes and granulocytes was the upregulation of CD11b expression, thereby increasing both the phagocytic potential and the ablility to induce diapedesis into inflammatory foci. The rich beta-glucan content of AbM could play a crucial role in this immune response.
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PMID:Effect of an extract of the mushroom Agaricus blazei Murill on expression of adhesion molecules and production of reactive oxygen species in monocytes and granulocytes in human whole blood ex vivo. 1755 Mar 80

Neonatal sepsis is a disease of infants who are less than 1 month of age. These infants are clinically ill, and their blood culture are positive for bacteria. The reported incidence of neonatal sepsis for all infants is 1 to 10 per 1000 live births. The mortality rate is 4.2-26%. The clinical signs are not specific and diagnosis of neonatal sepsis is one of the most difficult tasks in clinical medicine. The aim of this work was determination of CD11b sensitivity and specificity for early detection of neonatal sepsis. We studied 65 neonates with gestational age of 27 to 38 weeks who were suspected for sepsis within the 28 days of life. Whole blood was obtained from neonates to determine CD11b expression on peripheral blood neutrophils by flow cytometry. C-Reactive protein (CRP) was measured qualitatively. Neonates were divided into two groups. Classification was based on the result of the blood culture. In the sepsis group all of the neonates (n=8) showed positive blood culture and clinical symptoms. In the suspected group (n=57) the neonates showed clinical signs but blood cultures were negative. Sensitivity and specificity of CD11b were 75%, 100% respectively. Also positive and negative predictive values of CD11b were 100% and 86% respectively. Results of present study and previous studies showed that measurement of neutrophil surface markers can be useful for diagnosis of infection in the early phases. Also, the quantitative measurement of CRP in addition to CD11b further enhances the ability to diagnose infections and improves sensitivity and negative predictive value by 100%.
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PMID:Evaluation of CD11b expression on peripheral blood neutrophils for early detection of neonatal sepsis. 1756 10

Leukocyte adhesion deficiency type I (LAD I) is characterized by recurrent and fatal bacterial infections, and caused by the mutation of the CD18 gene. A 9-month-old infant whose umbilical cord separated at day 10 of life had sepsis, complicated otitis media and neutrophilia. Molecular analysis showed homozygous intron 7 (+1) g > a in the CD18 gene, resulting in three splicing transcriptions that inserted 64, 298 (5' end of intron 7), and 1157 (whole intron 7) nucleotides into the 300th amino acid of Ile and stopped at the 326th (inserted 64 and 1157 nucleotides) and the 344th (inserted 64 nucleotides), respectively. The two truncated mutations lost cysteine-rich, transmembrane, and cytoplasma domains. Increased susceptibility to infections correlated to polymorphonuclear cell dysfunction, including absent expression of adhesion molecule (CD11b/CD18), impaired chemotaxis, and decreased phagocytosis. Both his heterozygous parents revealed non-random skewing only to the wild type. The skewing pattern and severe phenotype make stem cell transplantation an optimal option.
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PMID:Neutrophil function and molecular analysis in severe leukocyte adhesion deficiency type I without separation delay of the umbilical cord. 1765 79

The pathogenesis of acute renal failure (ARF) occurring during the course of sepsis is incompletely understood. Intercellular adhesion molecule-1 (ICAM-1) is a key cell adhesion molecule upregulated by LPS, which binds to the integrins CD11a/CD18 and CD11b/CD18 present on the surface of leukocytes. We hypothesized that ICAM-1 facilitates renal injury in LPS-induced ARF. To test this, three groups of mice (n = 8 per group) were injected intraperitoneally with 6 mg/kg LPS: 1) normal C57BL/6 mice, 2) mice with a targeted deficiency of ICAM-1 (ICAM-1(-/-)), and 3) mice expressing very low levels of CD18 (CD18-def). ICAM-1(-/-) mice were significantly resistant to LPS-mediated ARF, as opposed to CD18-def mice, which developed severe ARF, as did wild-type controls (48 h blood urea nitrogen 143 +/- 31.5, 70.8 +/- 24.4, and 185 +/- 16.6 mg/dl in wild-type, ICAM-1(-/-), and CD18-def mice, respectively, P < 0.05). At death, ICAM-1(-/-) mice had significantly less renal neutrophil infiltration than the other two groups, as well as less histological tubular injury. Depletion of neutrophils with mAb Gr-1 led to a profound exaggeration of tumor necrosis factor (TNF) release and high mortality, but neutrophil-depleted mice receiving 10-fold less LPS were protected against ARF despite TNF release similar to what is normally associated with LPS-induced ARF. LPS caused a significant increase in renal expression of chemokines; however, this increase was significantly exaggerated in CD18-def mice, which may account for their lack of protection. In conclusion, these data show that ICAM-1 plays a key role in LPS-induced ARF.
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PMID:The role of ICAM-1 in endotoxin-induced acute renal failure. 1767 Aug 97

Insulin is essential for glucose homeostasis. Insulin/glucose-insulin-potassium (GIK) regimen suppresses the production of tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), macrophage migration inhibitory factor (MIF) and other pro-inflammatory cytokines and reactive oxygen species (ROS), enhances the synthesis of endothelial nitric oxide (eNO), and anti-inflammatory cytokines interleukins-4 (IL-4) and interleukin-10 (IL-10). In subjects who are critically ill, monocyte HLA-DR expression was significantly decreased with a concomitant increase in plasma IL-10 and IL-4 concentrations. Large increases in the plasma concentrations of TNF-alpha, IL-6, sustained increase in the expression of leukocyte CD11b/CD18, and ROS generation following surgery and infections were found to be associated with increased mortality. By virtue of its actions on pro- and anti-inflammatory cytokines and ROS, insulin may have the ability to alter HLA-DR expression in the critically ill and thus bring about its beneficial actions in sepsis/septic shock, myocardial recovery following acute myocardial infarction, improve prognosis of those who are critically ill, and suppress inflammation.
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PMID:Insulin in the critically ill with focus on cytokines, reactive oxygen species, HLA-DR expression. 1792 13


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