Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro pretreatment of human monocytes (MO) with low-dose lipopolysaccharide (LPSp) inhibits TNF release in response to subsequent LPSa activation. Septic patients are often indistinguishable from patients with systemic inflammatory response syndrome (SIRS). We hypothesized that in vivo exposure to "septic" stimuli impairs subsequent LPSa-stimulated MO TNF production in vitro. Human peripheral MO were obtained after informed consent from controls or patients with sepsis, SIRS, or posttrauma [ACCP/SCCM definitions]. Cells were plated in vitro, incubated 24 hr, and then stimulated with 0-1000 ng/ml LPSa for 4 hr. Parallel control MO were incubated in vitro with 100 ng/ml LPSp for 24 hr and then stimulated with 1000 ng/ml LPSa for 4 hr. Supernatant TNF (mean U/ml +/- SEM) was measured by bioassay. ANOVA was used to determine statistical significance. In vitro LPSp pretreatment markedly inhibited subsequent LPSa-stimulated TNF release. In vitro LPSa-stimulated TNF release was likewise significantly inhibited with MO from septic patients compared to controls. Inhibition was more profound in septic patients with shock (not shown). No impaired TNF release was seen with MO from SIRS or trauma patients. In conclusion, in vivo preexposure to inflammatory stimuli in septic patients alters monocyte regulation in a manner similar to in vitro endotoxin tolerance. Provocative in vitro monocyte LPS stimulation may distinguish patients with sepsis and SIRS.
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PMID:In vivo endotoxin tolerance: impaired LPS-stimulated TNF release of monocytes from patients with sepsis, but not SIRS. 920 54

High levels of nitric oxide (NO) have been reported in exhaled air of asthmatic individuals. Because alveolar macrophages (AM) are major producers of cytokines, and bronchoalveolar lavage fluid (BALF) from asthmatic individuals contains increased levels of inflammatory cytokines, this study was undertaken to determine whether NO modified the production of inflammatory cytokines by human AM. AM were obtained from normal volunteers by fiberoptic bronchoscopy. Tumor necrosis factor-alpha (TNF-alpha) production stimulated by lipopolysaccharide (LPS; 0.5 microg/ml) was measured with an enzyme-linked immunosorbent assay (ELISA). NO generated from 2,2-(hydroxynitrosohydrazono)-bis-ethanamine (DETA NONOate) (0.1 to 1.0 mM) inhibited TNF-alpha secretion in a dose-dependent manner. At 1 mM DETA NONOate, mean inhibition (+/- SEM) of TNF-alpha secretion was 56 +/- 4% (P = 0.002). To determine whether this effect was cytokine specific, interleukin-1beta (IL-1beta) and macrophage inflammatory protein-1alpha (MIP-1alpha) were evaluated, and DETA NONOate was also found to inhibit both of these cytokines. Basal cytokine levels from unstimulated AM were unaffected by NO. These findings indicate that NO is a potent inhibitor of cytokine production by stimulated human AM.
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PMID:Nitric oxide inhibits inflammatory cytokine production by human alveolar macrophages. 930 13

The protective efficacy of immunisation with heat-killed Pseudomonas aeruginosa on murine gut-derived sepsis was evaluated. Mice were immunised intraperitoneally six times with heat-killed bacteria. This induced mean (SEM) serum IgG and IgM antibodies of 1792 (374.7) and 37.3 (8.9) ELISA units, respectively. Specific pathogen-free mice given P. aeruginosa strain D4 orally died of bacteraemia after administration of cyclophosphamide. Immunisation with heat-killed bacteria significantly increased the survival rate compared with that of control mice immunised with bovine serum albumin. Macroscopic observation revealed marked production of liver abscesses in mice immunised with bovine serum albumin but not in those immunised with heat-killed bacteria. Only low titres of antibody against the exoenzymes alkaline protease, elastase and exotoxin A were observed, and no significant difference between antibody titres to boiled and unboiled suspensions of sonicated P. aeruginosa was detected. This suggests that the main protective antibodies might be those specific to the heat stable antigen (lipopolysaccharide). Immunisation with heat-killed bacteria provided complete protection against death from gut-derived P. aeruginosa sepsis.
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PMID:Effect of immunisation with Pseudomonas aeruginosa on gut-derived sepsis in mice. 956 94

We employed a bile duct ligation (BDL) model of cholestatic liver injury to test the hypothesis that this form of preexisting hepatic dysfunction alters the kinetics of circulating TNF-alpha and IL-6 after Escherichia coli endotoxemia, thereby augmenting mortality and lung injury by a TNF-alpha:leukotriene (LT) axis of inflammation. Male rats were catheterized 13 d after BDL or sham surgery and studied while awake 18 to 24 h later. Cholestasis after BDL was confirmed by baseline serum bilirubin (BDL = 7.34 +/- 0.72 mg/dl, mean +/- SEM, n = 17 versus Sham = 0.25 +/- 0.07, n = 20; p < 0.005) and histopathology. Sham and BDL animals received E. coli lipopolysaccharide serotype O55:B5 (LPS, 5 mg/kg i.v.) or 0.9% NaCl (NS) ending at t = 0 and were monitored over 24 h for vital signs and hemodynamics. In parallel studies, lipoxygenase inhibition was performed using diethylcarbamazine or the 5-lipoxygenase activating-protein inhibitor MK-886. Blood was collected at baseline and at t = 1.5, 3.5, and 24 h for formed elements and for serum endotoxin, TNF-alpha, IL-6, bilirubin, and alanine aminotransferase (ALT). Organs were evaluated at 24 h for histopathology, including neutrophil (PMN) densities and wet/dry weight (W/D) ratios. Cholestasis reduced survival after otherwise nonlethal endotoxemia, with seven of 11 BDL + LPS rats dying within 24 h versus no deaths in BDL + NS (n = 6), Sham + LPS (n = 14), or Sham + NS (n = 6) animals (p < 0.01). Despite equivalent serum endotoxin between groups, circulating TNF-alpha was 8-fold higher in BDL + LPS than in Sham + LPS rats at 1.5 and 3.5 h (p < 0.001), whereas serum TNF-alpha did not differ between BDL + NS and Sham + NS rats. IL-6 likewise was increased differentially by 1.5 h in BDL + LPS animals (11.98 +/- 2.42 ng/ml) versus Sham + LPS rats (3.05 +/- 0.58 ng/ml, p < 0.05). Hypothermia, bradycardic hypotension, and leukopenia were most severe and prolonged in BDL + LPS rats, which also had significantly higher ALT values, W/D ratios, and organ PMN counts. LT inhibition failed to reduce BDL-related differences in serum cytokines or survival after endotoxemia. Thus, cholestasis augments inflammatory responses to gram-negative endotoxemia, sensitizing the host to enhanced fluid flux in multiple organs and to mortality by a LT-independent mechanism.
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PMID:Cholestatic liver injury increases circulating TNF-alpha and IL-6 and mortality after Escherichia coli endotoxemia. 960 37

This study examined whether pretreating rats with endotoxin (lipopolysaccharide, LPS) modifies the retardation of the gastric emptying of liquids induced by this same toxin. Male SPF Wistar rats (8-10 weeks old, 230-300 g) were divided into four groups of eight animals each that received either the vehicle solution sterile pyrogen free saline or LPS (50 mg/kg, intravenously), 96 and 5 hours before the measurement of gastric emptying. The four groups were defined on the basis of the sequence of intravenous injections namely saline + saline, saline + LPS, LPS + saline, and LPS + LPS. All the animals were fasted for 24 hours before and after the first injection and then received food ad libitum for the next 48 hours, before being fasted again for 24 hours prior to the evaluation of gastric emptying. Throughout these periods, the rats had free access to water that was only withdrawn 1 h before the study. A saline solution containing red phenol was used as the test meal. Gastric retention (GR) was measured between 2 and 4 p.m. 120 minutes after the orogastric administration of the meal. The results showed that in the saline + LPS group the GR (mean +/_ SEM = 61.1 +/_ 2.6%) was significantly greater (P < 0.05, Tukey test) than in relation to the saline + saline group (40.5 +/_ 2.6%). On the other hand, there were no significantly differences between the animals which received LPS + LPS (41.8 +/_ 2.5%) and those receiving LPS + saline (37.5 +/- 1.8%) or between these the groups and those receiving saline on both occasions. In conclusion the pretreatment with LPS suppressed the effect of endotoxin on gastric emptying by inducing early tolerance in the motor activity of the stomach in a manner similar to that described for other systems
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PMID:Effect of tolerance to bacterial lipopolysaccharide on gastric emptying in rats. 962 17

We have previously shown that Curosurf, a natural porcine surfactant, and its phospholipids effectively suppressed secretion of tumor necrosis factor (TNF-alpha) by resting and through lipopolysaccharide (LPS)-stimulated human monocytes. In this study the effect of Curosurf on monocyte mRNA for TNF-alpha and TNF-alpha type II-receptor (TNF-alpha-RII) were analyzed to evaluate the cellular mechanisms involved in the modulation of TNF-alpha expression. LPS-stimulated monocytes simultaneously exposed to Curosurf (500 microg/mL for 24 h) expressed approximately 70% less TNF-alpha mRNA when compared with control subjects (p < 0.05). In addition, 86% less TNF-alpha RII mRNA was found in monocytes exposed to Curosurf (p < 0.001). Decreased mRNA expression was clearly associated with significantly reduced secretion of TNF-alpha protein (Curosurf-exposed LPS-stimulated monocytes 3628 +/- 1873 pg/mL TNF, LPS-stimulated monocytes 31,376 +/- 2524 pg/mL TNF; mean +/- SEM, p < 0.001). The activation of the transcription factor nuclear factor-kappaB upon LPS stimulation is not affected by Curosurf incubation. This excludes that the decrease in mRNA and protein levels of TNF-alpha and TNF-alpha-RII is due to an inhibition of nuclear factor-kappaB activation by Curosurf. We conclude that Curosurf affects TNF-alpha release of LPS-stimulated monocytes at a pretranslational site by down-regulating both mRNA for TNF-alpha and TNF-alpha-RII, therefore acting as an anti-inflammatory agent within alveolar space.
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PMID:Natural porcine surfactant (Curosurf) down-regulates mRNA of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha type II receptor in lipopolysaccharide-stimulated monocytes. 966 67

Nitric oxide (NO), produced by alveolar macrophages (AM) is used as a marker of respiratory tract inflammation. Lipocortin 1 (Lc-1) is an anti-inflammatory, glucocorticoid-inducible protein. The current aims were to determine whether (a) an Lc-1-derived peptide, Ac2-26, inhibited lipopolysaccharide (LPS)-induced NO release by primary AM in vitro and (b) the inhibitory action of dexamethasone was Lc-1-dependent. LPS treatment stimulated NO release from rat AM. Ac2-26 had little effect on unstimulated release, but suppressed LPS-stimulated release at concentrations > or =320 nM (320 nM, 10 +/- 3%; 3.2 microM, 15 +/- 3%; 32 microM, 27 +/- 4% NO inhibited, mean +/- SEM, n = 6). Inhibition by dexamethasone of NO release was unaffected by neutralizing anti-Lc-1 indicating that this action is Lc-1-independent in primary AM. Nevertheless inhibition of NO release by Ac2-26 (80 microM) was similar to that of 1 microM dexamethasone (Ac2-26, 40 +/- 6%; dexamethasone, 48 +/- 6% NO inhibited, mean +/- SEM, n = 6).
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PMID:Reduction of nitric oxide release from alveolar macrophages by a lipocortin peptide. 983 95

To investigate the immune environment of the peritoneal cavity, ICAM-1 (intercellular adhesion molecule) expression on the apical surface of the hepatic peritoneum of LPS (lipopolysaccharide) stimulated rats was analyzed ultrastructurally and chronologically with immunoTEM&SEM. ICAM-1 expression was restricted to the side of microvilli of the mesothelial cells. Microvilli demonstrated bulbous tips and included fuzzy coats and strands. Bulbous tips sometimes expressed the antigen, but fuzzy coats and strands did not. Intervillar cell surfaces lacked its expression. Although ICAM-1 expression increased eightfold 24 hr after stimulation, the selective expression remained unchanged. These results suggest that microvilli are closely associated with cell migration in the peritoneal cavity through adhesion molecules that establish a road for migration.
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PMID:Abdominal peritoneum as a defense organ: analysis of ICAM-1 expression in the LPS-stimulated rat. 989 Jul 26

To examine whether endotoxaemia accompanying long-term, strenuous physical exercise is involved in exercise-induced increase in plasma tumour necrosis factor alpha (TNF-alpha) concentration and polymorphonuclear neutrophil (PMN) activation, 14 male recreational athletes [mean age 28 (SEM 1) years] were studied. Exercise consisted of a 1.5-km river swim, a 40-km bicycle race, and a 10-km road race. Mean time to complete the race was 149.8 (SEM 4.8) min. The plasma concentrations of granulocyte myeloperoxidase (MPO) and TNF-alpha were significantly higher than baseline values immediately and 1 h after exercise (P<0.001). Both variables returned to pre-race levels the day after exercise. Marked, transient decreases in plasma concentrations of anti-lipopolysaccharide (LPS) immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies directed against a panel of selected smooth gram-negative LPS were observed after the race, reaching in most cases minimal values in the blood sample drawn immediately following the completion of the triathlon. There was no significant correlation between the magnitude of PMN activation, as assessed by the increase in plasma concentrations of MPO, and the humoral markers of endotoxaemia and TNF-alpha. An inverse, highly significant relationship between the increase in plasma TNF-alpha concentrations and the changes in circulating anti-LPS IgM antibodies concentrations was observed (r = -0.7; P<0.01). These findings suggest that exercise-induced endotoxaemia was involved in the release of TNF-alpha, that the magnitude of the TNF-alpha response to exercise was down-regulated by anti-LPS antibodies of the IgM class, and that the production of TNF-alpha and endotoxaemia did not seem to play a role in the activation of circulating PMN in the exercising subjects.
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PMID:Endotoxaemia, production of tumour necrosis factor alpha and polymorphonuclear neutrophil activation following strenuous exercise in humans. 1005 62

We investigated whether cytokines produced primarily by monocytes/macrophages (IL-1alpha), Th1-lymphocytes (IFNgamma), or Th2-lymphocytes (IL-4) are modulated in diabetes-prone NOD mice by insulin treatment as used in prophylaxis studies. The cytokines were measured by ELISA in plasma and in supernatants of spleen cells activated ex vivo by lipopolysaccharide plus phytohemagglutinin. Insulin, 0.25-0.50 IU/day, was given subcutaneously for 8 weeks starting in 4-week-old female mice. The insulin-treated and control NOD mice showed similar weight gains and, by the end of the study, both groups exhibited cell infiltration in about 25% of their islets. IL-1alpha, IFNgamma and IL-4 were generally below detection in plasma of prediabetic animals and controls. Diabetic NOD mice, aged 28-45 weeks, had significantly elevated plasma IL-1alpha: 154+/-39 pg/ml (mean+/-SEM, p<0.0001). While ex vivo activated NOD splenocytes released similar amounts of IL-1alpha, insulin therapy increased the levels from 99+/-17 to 155+/-19 pg/10(6) cells (p<0.05). Supernatants of activated splenocytes from prediabetic NOD mice had lower levels of IL-4 (<15 pg/10(6) cells) compared with those from BALB/c mice (88+/-22 pg/10(6) cells; p<0.01), and this deficiency was partially compensated for when the NOD mice were given insulin (27+/-8; p<0.01). The levels of IFNgamma were comparable and largely unaffected by insulin treatment. Hence, insulin therapy appears to partially normalize an otherwise deficient Th2 response in NOD mice.
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PMID:Cytokine production in NOD mice on prophylactic insulin therapy. 1023 Jun 96


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