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)

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

Intercellular adhesion molecule-1 (ICAM-1) is involved in neutrophil transmigration across endothelium during sepsis-induced acute lung injury and anti-ICAM-1 interventions may represent new strategy of pulmonary protection. Haem oxygenase-1 (HO-1) has been demonstrated to exert anti-inflammatory actions via decrease of expression of adhesion molecules. We investigated the role of HO-1 in the action of curcumin, a naturally occurring yellow pigment isolated from plant Curcuma longa L., on ICAM-1 expression in tumour necrosis factor-alpha-stimulated EA.hy926 cells and lungs of lipopolysaccharide-treated mice. Both, in vitro and in vivo curcumin induced HO-1 and curcumin-elicited induction of HO-1 was associated with inhibition ICAM-1 expression. Moreover, curcumin significantly inhibited pulmonary sequestration of leucocytes in response to lipopolysaccharide as evidenced by decrease of myeloperoxidase activity in lung tissue. Both in vitro and in vivo effects of curcumin were reversed by an inhibitor of HO activity, chromium (III) mesoporphyrin IX chloride. We conclude that induction of HO-1, via decrease of endothelial ICAM-1, plays a pivotal role in curcumin-dependent prevention of pulmonary sequestration of neutrophils in a mouse model of endotoxaemia.
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PMID:The role of haem oxygenase-1 in the decrease of endothelial intercellular adhesion molecule-1 expression by curcumin. 1797 99

Recent studies suggest that exogenously administered CO is beneficial for the resolution of acute inflammation. In this study, we assessed the role of CO liberated from a systemically administered tricarbonyldichlororuthenium-(II)-dimer (CORM-2) on modulation of liver inflammation during sepsis. Polymicrobial sepsis in mice was induced by cecal ligation and perforation (CLP). CORM-2 (8 mg/kg iv) was administered immediately after CLP induction, and neutrophil [polymorphonuclear leukocyte (PMN)] tissue accumulation, activation of transcription factor, NF-kappaB, and changes in adhesion molecule ICAM-1 expression (inflammation-relevant markers) were assessed in murine liver 24 h later. In addition, the effects and potential mechanisms of CORM-2-released CO in modulation of vascular endothelial cell proinflammatory responses were assessed in vitro. To this end, human umbilical vein endothelial cells (HUVEC) were stimulated with LPS (1 microg/ml) in the presence or absence of CORM-2 (10-100 microM) and production of intracellular reactive oxygen species (ROS), (DHR123 oxidation) and NO (DAF-FM nitrosation) and subsequent activation of NF-kappaB were assessed 4 h later. In parallel, expression of ICAM-1 and inducible NO synthase (iNOS) proteins along with PMN adhesion to LPS-challenged HUVEC were also assessed. Induction of CLP resulted in increased PMN accumulation, ICAM-1 expression, and activation of NF-kappaB in the liver of septic mice. These effects were significantly attenuated by systemic administration of CORM-2. In in vitro experiments, CORM-2-released CO attenuated LPS-induced production of ROS and NO, activation of NF-kappaB, increase in ICAM-1 and iNOS protein expression and PMN adhesion to LPS-stimulated HUVEC. Taken together, these findings indicate that CO released from systemically administered CORM-2 provides anti-inflammatory effects by interfering with NF-kappaB activation and subsequent downregulation of proadhesive vascular endothelial cell phenotype in the liver of septic mice.
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PMID:Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice. 1799 8

Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. A hallmark of these endovascular S. aureus infections is that the coagulation system is triggered by a tissue factor (TF)-dependent pathway. This study demonstrates that highly purified S. aureus peptidoglycan, lipoteichoic acid (LTA) and TSST-1 increase TF mRNA and TF surface protein in human umbilical vein endothelial cells (ECs). Concomitantly, peptidoglycan- and LTA-activated ECs express significant TF-dependent procoagulant activity (TF PCA). In addition peptidoglycan, but not LTA or TSST-1, induced surface expression of the EC inflammation markers ICAM-1 and VCAM-1, which supported the adhesion of monocytes to these ECs. During the coculture of peptidoglycan-activated ECs and adherent monocytes, a marked additional increase of TF PCA was observed. Marginal increases in TF PCA were observed in cocultures of monocytes with LTA- or TSST-1-activated ECs. This study defines in particular staphylococcal peptidoglycan, previously known as a potent initiator of TF PCA in monocytes, as also being an activator of a coagulant response in human ECs that is further intensified by the presence of surface-bound monocytes.
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PMID:Staphylococcal peptidoglycan initiates an inflammatory response and procoagulant activity in human vascular endothelial cells: a comparison with highly purified lipoteichoic acid and TSST-1. 1803 38

Endotoxin is a major cause of endotoxinemia, sepsis, and pneumonia due to gram-negative bacteria. Experimental endotoxin administration via the tracheal route has been extensively used to study the biological and pathophysiologic pathways of inflammation. In particular, experimental endotoxin instillation in the respiratory tree has allowed an extended research with regard to the local response of the lungs to the pathogenic stimulus. This study aims (a) to define early events in the inflammatory cascade and (b) to evaluate the efficacy of adrenaline to ameliorate the acute pulmonary inflammation in vivo after administration of intratracheal lipopolysaccharide (LPS) in an in vivo animal model. Two groups of animals were used for that purpose, a control group (single LPS administration) and a study group (subcutaneous adrenaline infusion following LPS administration). We found that mononuclear recruitment, along with an increased population of CD4+ T lymphocytes, is an early event during the course of LPS-challenged inflammation. In the study group, we determined that adrenaline mediated the lung inflammation in a statistically significant degree. By the use of immunohistochemistry, we identified (1) an increased population of CD4+ T lymphocytes in the inflammatory infiltrate, further endorsing the hypothesis that T-helper lymphocytes, along with macrophages, secrete cytokines which amplify the inflammatory response, and (2) an upregulation of ICAM-1 expression, suggesting an important role in the early pathogenesis of LPS-induced acute lung injury. Our study establishes that systemic adrenaline administration after LPS instillation may ameliorate the inflammatory lung response in vivo.
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PMID:Adrenaline attenuates the acute lung injury after intratracheal lipopolysaccharide instillation: an experimental study. 1830 52

This study investigated the effects of fish oil on adhesion molecule expression and tissue myeloperoxidase (MPO) activity in hypercholesterolemic mice with sepsis. There were one control and two experimental groups in this study. The control group (C) was fed a regular chow diet for 7 weeks, while hypercholesterolemia in the experimental group was induced by feeding a high-fat diet (20%, w/w) with cholesterol (2%, w/w) for 4 weeks. Then the experimental group was divided into two subgroups with identical nutrient distributions except that one subgroup was fed soybean oil (SO), while part of the soybean oil was replaced by fish oil (FO) in the other one for 3 weeks. After feeding the diets for 7 weeks, sepsis was induced in all three groups by cecal and ligation and puncture (CLP), and mice were sacrificed at 0, 6 or 24 h after CLP, respectively. The results showed that the FO group had a higher intracellular interferon-gamma/interleukin-4 ratio and lower tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations in peritoneal lavage fluid at 6 h after CLP than those in the C and SO groups. Lymphocyte CD11a/CD18 expressions were higher at 0 and 6 h and neutrophil CD11b/CD18 were higher at 6 h in the SO group than in the FO and C groups. The SO group had higher plasma intercellular adhesion molecule (ICAM)-1 levels than C group at 0 and 6 h, whereas no difference in ICAM-1 concentrations were observed between the C and FO groups at 0 h after CLP. Hypercholesterolemia resulted in higher tissue MPO activities. There were no differences in MPO activities in various organs between the two experimental groups. These results suggest that hypercholesterolemic mice fed FO did not exhibit immunosuppression when complicated with sepsis. FO administration reduced adhesion molecule expressions and inflammatory-related mediators at the site of injury at an early but not a late stage of sepsis. However, compared with the SO group, the influences of FO on MPO activities in various organs were not obvious in hypercholesterolemic mice with sepsis.
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PMID:Effects of dietary fish oil supplementation on cellular adhesion molecule expression and tissue myeloperoxidase activity in hypercholesterolemic mice with sepsis. 1860 12

Sepsis is a multifactorial, and often fatal, disorder typically characterized by widespread inflammation and immune activation with resultant endothelial activation. In the present study, we postulated that the adipokine adiponectin serves as a critical modulator of survival and endothelial activation in sepsis. To this aim, we evaluated both loss-of-function (adiponectin gene-deficient mice) and subsequent gain-of-function (recombinant adiponectin reconstitution) strategies in two well-established inflammatory models, cecal ligation perforation (CLP) and thioglyocollate-induced peritonitis. Adipoq(-/-) mice, subjected to CLP, exhibited a profound ( approximately 8-fold) reduction in survival compared with their wild-type Adipoq(+/+) littermates after 48 h. Furthermore, compared with wild-type controls, thioglycollate challenge resulted in a markedly greater influx of peritoneal neutrophils in Adipoq(-/-) mice accompanied by an excess production of key chemoattractant cytokines (IL-12p70, TNFalpha, MCP-1, and IL-6) and upregulation of aortic endothelial adhesion molecule VCAM-1 and ICAM-1 expressions. Importantly, all of these effects were blunted by recombinant total adiponectin administration given 3 days prior to thioglycollate challenge. The protective effects of adiponectin were ascribed largely to higher-order adiponectin oligomers, since administration of recombinant C39A trimeric adiponectin did not attenuate endothelial adhesion molecule expression in thioglycollate-challenged Adipoq(-/-) mice. These data suggest a critical role of adiponectin as a modulator of survival and endothelial inflammation in experimental sepsis and a potential mechanistic link between adiposity and increased sepsis.
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PMID:Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality. 1917 45

Chronic kidney disease (CKD) carries an increased risk of cardiovascular disease (CVD). Macrophage migration inhibiting factor (MIF) is a proinflammatory cytokine implicated in the pathogenesis of sepsis, autoimmune disease, atherogenesis, and plaque instability, and is a known cardiac depressant. This post-hoc, cross-sectional study examined whether MIF serum concentrations are elevated in CKD patients. Our study included CKD 3-5 patients with moderate to severe renal dysfunction (n = 257) (mean age SD; 55 +/- 12 years) and 53 controls (60 +/- 12 years). Serum MIF concentrations, measured by enzyme-linked immunosorbent assay (ELISA), were studied in relation to glomerular filtration rate (GFR), presence of CVD, outcome and inflammatory and oxidative stress markers. MIF was significantly elevated in CKD patients compared with controls (CKD: median 676 [range 118-8275 pg/mL] controls: 433 [142-4707] pg/mL; P = 0.008). MIF was also associated with 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels (rho = 0.26; P = 0.001), a marker of oxidative stress, and ICAM-1 levels (rho = 0.14; P = 0.02), a marker of endothelial activation. However, the elevated MIF concentrations were neither correlated with glomerular filtration rate (GFR) nor inflammatory markers such as CRP, IL-6, and TNF. When combining MIF and IL-6 as a marker of inflammation, a significant increase in risk for CVD was found, but when analyzing all-cause mortality, this did not differ significantly with regard to mortality from inflamed patients with low MIF levels. The data suggest that increased serum MIF levels found in CKD is not caused primarily by poor renal function, but is associated with markers of oxidative stress and endothelial activation and may play a role in vascular disease associated with CKD.
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PMID:Elevated serum macrophage migration inhibitory factor (MIF) concentrations in chronic kidney disease (CKD) are associated with markers of oxidative stress and endothelial activation. 1908 68

Hypervirulent MenB causing fatal human infections frequently display the oligomeric-coiled coil adhesin NadA, a 45-kDa intrinsic outer membrane protein implicated in binding to and invasion of respiratory epithelial cells. A recombinant soluble mutant lacking the 10-kDa COOH terminal membrane domain (NadA(Delta351-405)) also activates human monocytes/macrophages/DCs. As NadA is physiologically released during sepsis as part of OMVs, in this study, we tested the hypothesis that NadA(+) OMVs have an enhanced or modified proinflammatory/proimmune action compared with NadA(-) OMVs. To do this we investigated the activity of purified free NadA(Delta351-405) and of OMVs from MenB and Escherichia coli strains, expressing or not full-length NadA. NadA(Delta351-405) stimulated monocytes and macrophages to secrete cytokines (IL-1beta, TNF-alpha, IL-6, IL-12p40, IL-12p70, IL-10) and chemokines (IL-8, MIP-1alpha, MCP-1, RANTES), and full-length NadA improved MenB OMV activity, preferentially on macrophages, and only increased cytokine release. NadA(Delta351-405) induced the lymphocyte costimulant CD80 in monocytes and macrophages, and NadA(+) OMVs induced a wider set of molecules supporting antigen presentation (CD80, CD86, HLA-DR, and ICAM-1) more efficiently than NadA(-) OMVs only in macrophages. Moreover, membrane NadA effects, unlike NadA(Delta351-405) ones, were much less IFN-gamma-sensitive. The activity of NadA-positive E. coli OMVs was similar to that of control OMVs. NadA in MenB OMVs acted at adhesin concentrations approximately 10(6) times lower than those required to stimulate cells with free NadA(Delta351-405).
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PMID:The membrane expression of Neisseria meningitidis adhesin A (NadA) increases the proimmune effects of MenB OMVs on human macrophages, compared with NadA- OMVs, without further stimulating their proinflammatory activity on circulating monocytes. 1940 83

Environmental hyperthermia and exercise produce extensive changes in gene expression in human blood cells, but it is unknown whether this also happens during febrile-range hyperthermia. We tested the hypothesis that heat shock protein (HSP) and immunomodulatory stress gene expression correlate with fever in intensive care unit patients. Whole blood messenger RNA was obtained over consecutive days from 100 hospitalized patients suffering from sepsis or noninfectious systemic inflammatory response syndrome (SIRS) as defined by conventional criteria. The most abnormal body temperature in the preceding 24 h was recorded for each sample. Expression analysis was performed using the Affymetrix U133 chip. ANCOVA followed by correlation analysis was performed on a subset of 278 prospectively identified sequences of interest. Temperature affected expression of 60 sequences, either independently or as a function of clinical diagnosis. Forty-eight of these (representing 38 genes) were affected by temperature only, including several HSPs, transcription factors heat shock factor (HSF)-1 and HSF-4, cellular adhesion molecules such as ICAM1/CD54 and JAM3, toll receptors TLR-6 and TLR-7, ribosomal proteins, and a number of molecules involved in inflammatory pathways. Twelve sequences demonstrated temperature-dependent responses that differed significantly between patients with sepsis and noninfectious SIRS: CXCL-13; heat shock proteins DNAJB12 and DNAJC4; the F11 receptor; folate hydrolase 1; HSF-2; HSP 70 proteins HSPA1A, HSPA1B, and HSPA1L; interleukin 8; lipopolysaccharide binding protein; and prostaglandin E synthase. Febrile-range temperatures achieved during sepsis and noninfectious SIRS correlate with detectable changes in stress gene expression in vivo, suggesting that fever can activate HSP gene expression and modify innate immune responses. For some genes, it appears that clinical condition can alter temperature-sensitive gene expression. Collectively, these data underscore the potential importance of body temperature in shaping the immune response to infection and injury.
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PMID:Core temperature correlates with expression of selected stress and immunomodulatory genes in febrile patients with sepsis and noninfectious SIRS. 1949 26

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