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Endotoxin
Kinds of Endotoxin Terms modified by Endotoxin Selected AbstractsAdenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteersACTA PHYSIOLOGICA, Issue 1 2009A. Soop Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source] FGF-2, IL-1, and TGF-, regulate fibroblast expression of S100A8FEBS JOURNAL, Issue 11 2005Farid Rahimi Growth factors, including fibroblast growth factor-2 (FGF-2) and transforming growth factor-, (TGF-,) regulate fibroblast function, differentiation and proliferation. S100A8 and S100A9 are members of the S100 family of Ca2+ -binding proteins and are now accepted as markers of inflammation. They are expressed by keratinocytes and inflammatory cells in human/murine wounds and by appropriately activated macrophages, endothelial cells, epithelial cells and keratinocytes in vitro. In this study, regulation and expression of S100A8 and S100A9 were examined in fibroblasts. Endotoxin (LPS), interferon , (IFN,), tumour-necrosis factor (TNF) and TGF-, did not induce the S100A8 gene in murine fibroblasts whereas FGF-2 induced mRNA maximally after 12 h. The FGF-2 response was strongly enhanced and prolonged by heparin. Interleukin-1, (IL-1,) alone, or in synergy with FGF-2/heparin strongly induced the gene in 3T3 fibroblasts. S100A9 mRNA was not induced under any condition. Induction of S100A8 in the absence of S100A9 was confirmed in primary fibroblasts. S100A8 mRNA induction by FGF-2 and IL-1, was partially dependent on the mitogen-activated-protein-kinase pathway and dependent on new protein synthesis. FGF-2-responsive elements were distinct from the IL-1,-responsive elements in the S100A8 gene promoter. FGF-2-/heparin-induced, but not IL-1,-induced responses were significantly suppressed by TGF-,, possibly mediated by decreased mRNA stability. S100A8 in activated fibroblasts was mainly intracytoplasmic. Rat dermal wounds contained numerous S100A8-positive fibroblast-like cells 2 and 4 days post injury; numbers declined by 7 days. Up-regulation of S100A8 by FGF-2/IL-1,, down-regulation by TGF-,, and its time-dependent expression in wound fibroblasts suggest a role in fibroblast differentiation at sites of inflammation and repair. [source] Characterization and Variability of Endotoxin and 3-Hydroxy Fatty Acids in an Office Building During a Particle Intervention StudyINDOOR AIR, Issue 1 2000Cynthia J. Hines Abstract Air and dust samples were collected on two floors of an office building during a double-blind particle intervention study to examine spatial and temporal variability of airborne endotoxin over a period of weeks, and to characterize endotoxin activity and lipopolysaccharide (LPS) content in carpet and chair dust. Air samples were collected on multiple days within and across weeks. Dust samples were collected from carpets and chairs one day per week for three weeks. Endotoxin was measured using a Limulus assay. Dust samples were analyzed for LPS by determination of 3-hydroxy fatty acids (3-OHFAs) using gas chromatography-mass spectrometry. The geometric mean (geometric standard deviation) for 96 indoor air samples was 0.24 (1.6) EU/m3. Significant within-floor spatial variation of airborne endotoxin was found (P<0.0001, n=80). Temporal variability of airborne endotoxin was not significant across weeks. Mean (±SD) endotoxin levels in carpet dust (59±9.3 EU/mg dust, n=12) and in chair dust (38±7.7 EU/mg dust, n=10) were significantly different (P<0.001). Carbon chain length-dependent differences in 3-OHFA levels by dust source and floor were found. Enhanced air filtration did not significantly affect airborne endotoxin (P=0.62); however, total dust mass and total endotoxin in carpet dust samples increased significantly after enhanced surface cleaning (P<0.01). These findings suggest that spatial variability, dust source, and surface cleaning may influence building occupant exposures to endotoxin., [source] Endotoxin increases hepatic susceptibility to lipid peroxidation: A possible role of ironJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2004W. Ibrahim Abstract The purpose of this study was to investigate the possible mechanism by which endotoxin enhances peroxidative damage to membrane lipids. Male B6C3 mice were treated with endotoxin intraperitoneally 0 or 20 mg/kg body weight for 24 h. Freshly prepared liver homogenate was incubated with either 1,5 mM of reduced glutathione (GSH), glucose, H2O2, ascorbic acid (AA), FeSO4, FeCl3, EDTA, FeCl3 plus AA, AA plus EDTA or EDTA plus FeCl3 in phosphate-buffered saline (PBS), pH 7.0, or PBS, at 37°C for 60 min. The levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), were significantly higher in the liver of endotoxin-treated mice, and the values were markedly increased following incubation. Compared to PBS, incubation with H2O2, FeCl3, FeSO4, and AA, but not glucose, significantly enhanced TBAR formation. The greatest increase of TBAR was found when AA and FeCl3 were added together. On the other hand, EDTA and GSH inhibited the formation of TBAR during incubation. When added before AA, EDTA completely inhibited the peroxidative effect of AA or FeSO4, and when added subsequent to AA, EDTA partially prevented the adverse effect of AA. The results obtained suggest that ionic iron plays an important role in initiating endotoxin-induced peroxidative damage to membrane lipids, and that AA may be involved in releasing iron from its protein complex and/or maintaining ionic iron in a reduced or catalytic state. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:23,29, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20002 [source] Endotoxin translocation in two models of experimental acute pancreatitisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2003C. Vasilescu Abstract To test the hypothesis that endotoxin is absorbed from the gut into the circulation in rats with experimental acute pancreatitis we studied two different animal models. In the first model necrotizing pancreatitis was induced by the ligation of the disatl bilio-pancreatic duct while in the second, experimental oedematous acute pancreatitis was induced by subcutaneous injections of caerulein. In both experiments, in the colon of rats with acute pancreatitis endotoxin from Salmonella abortus equi was injected. Endotoxin was detected by immunohistochemistry in peripheral organs with specific antibodies. The endotoxin was found only in rats with both acute pancreatitis and endotoxin injected into the colon and not in the control groups. The distribution of endotoxin in liver at 3 and 5 days was predominantly at hepatocytes level around terminal hepatic venules, while in lung a scattered diffuse pattern at the level of alveolar macrophages was identified. A positive staining was observed after 12 hours in the liver, lung, colon and mesenteric lymph nodes of rats with both caerulein pancreatitis and endotoxin injected into the colon. We conclude that the experimental acute pancreatitis leads to early endotoxin translocation from the gut lumen in the intestinal wall and consequent access of gut-derived endotoxin to the mesenteric lymph nodes, liver and lung. [source] The Phosphodiesterase III Inhibitor Olprinone Decreases Sensitivity of Rat Kupffer Cells to EndotoxinALCOHOLISM, Issue 2004Nobuyuki Enomoto Background: Sensitivity of Kupffer cells to endotoxin [lipopolysaccharide (LPS)] and overproduction of tumor necrosis factor-, (TNF-,) are critical for progression of alcoholic liver injury. Therefore, suppression of TNF-, should prove useful for treatment of alcoholic liver injury. However, a transient increase of intracellular calcium ([Ca2+]i) is required for LPS-induced TNF-, production by the macrophage cell line. The phosphodiesterase III inhibitor olprinone has been shown to suppress [Ca2+]i level in vascular smooth muscle cells. Accordingly, the purpose of this study was to determine whether olprinone could prevent sensitization of Kupffer cells to endotoxin. Methods: Kupffer cells were isolated by collagenase digestion and differential centrifugation. LPS was added to Kupffer cells 24 hr after incubation with or without olprinone (0.1 ,mol/liter). After addition of LPS (10 ,g/ml) to culture media, [Ca2+]i was measured using a fluorescent indicator, fura-2. Results: LPS increased [Ca2+]i of Kupffer cells in control rats from basal levels (28 ± 4 nmol/liter) to 280 ± 14 nmol/liter. This increase was blunted by olprinone (91 ± 8 nmol/liter). Similarly, olprinone diminished the LPS (1 ,g/ml)-induced TNF-, production by Kupffer cells by 30% (2220 ± 116 vs. 1386 ± 199 pg/ml; p < 0.05). Conclusions: These results indicate that olprinone decreases sensitivity of Kupffer cells to endotoxin. [source] Effect of Acute Ethanol Administration on the Intestinal Absorption of Endotoxin in RatsALCOHOLISM, Issue 3 2000Hironao Tamai Background: Endotoxin has been implicated in the pathogenesis and progression of alcoholic liver disease. Not only inactivation of reticuloendothelial function, which reduces clearance of endotoxin, but also an increase in absorption of endotoxin from the intestine may be involved in mechanisms of ethanol-induced endotoxemia. However, it is unclear how ethanol affects absorption of endotoxin from the intestine in vivo. Methods: We gave 10 mg/kg of lipopolysaccharides to rats with water (group 1), 5% ethanol (group 2), or 20% ethanol (group 3) using an intubation tube to the stomach. Blood samples were collected and plasma endotoxin levels were measured. We used fluorescence spectrophotometer to examine permeability of the gut to macromolecules (fluorescein isothiocyanate-dextran; 4,000 Da [FD4] or 20,000 Da [FD20]). Results: Plasma endotoxin levels were not different between group 1 (9 ± 2 pg/ml) and group 2 (14 ± 3 pg/ml), whereas they significantly increased in group 3 with a peak at 60 min (87 ± 35 pg/ml). Acute ethanol administration did not affect clearance of endotoxin in rats. Hemorrhagic erosions of the proximal small intestine with epithelial cell loss were observed in group 3 at 4 hr, but no significant histological change was observed at 30 min by light microscopy. Acute ethanol administration (20%) increased the permeability of the small intestine to FD4 and FD20 in 30 min when no hemorrhagic erosions of the proximal small intestine with epithelial cell loss were observed. Conclusions: Acute ethanol administration increases intestinal permeability before pathological changes are revealed by light microscopy. Acute ethanol ingestion, especially at high concentrations, facilitates the absorption of endotoxin from rats' small intestine via an increase in intestinal permeability, which may play an important role in endotoxemia observed in alcoholic liver injury. [source] Influence of endotoxin on the disposition kinetics and dosage regimens of oxytetracycline in calvesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2003R. Kumar The influence of endotoxin on the disposition kinetics of oxytetracycline (OTC) (10 mg/kg) was investigated in five healthy ruminating male crossbred calves. The serum concentration-time data of OTC before and after endotoxin challenge were best described by a two-compartment open model. Repeated administration of Escherichia coli endotoxin (1 ,g/kg, i.v.) at an interval of 12 h up to 48 h produced a clear rise in the body temperature and an increase in the pulse and respiration rates. Endotoxin caused a significant reduction in mean transit time in tissue compartment (MTTT) (P , 0.05), mean residence time in the peripheral tissue compartment (MRTT) (P , 0.05), mean residence time in the body (MRTB) (P , 0.05), elimination half-life (t1/2,2) (P , 0.05) and distribution space in tissues (VT) (P , 0.01) and at steady-state (Vd(ss)) (P , 0.01). Endotoxin had no effect on the distribution clearance (ClD), systemic clearance (Cl) and distribution half-life of OTC, while the values of first order rate constant of transfer of drug from tissue to central compartment (K21) and the zero time intercept at terminal phase (C2) were significantly high. The drug dosage regimens to maintain serum OTC concentrations of 0.5, 1, 2, 4, 6 and 8 ,g/mL were also determined in febrile and clinically healthy animals. [source] The role of parasitic infections in atopic diseases in rural schoolchildrenALLERGY, Issue 8 2006B. Karadag Background:, There is increasing evidence that the farming environment has a protective effect as regards allergic diseases. Exposure to animal parasites, particularly helminth infections, is common in the farming environment. However, the role of helminths in this environment is not well determined to date. Methods:, This analysis focuses on 613 children 6,13 years of age from rural areas of Austria, Germany and Switzerland, who took part in the Allergy and Endotoxin (ALEX) study. Allergic diseases and farming characteristics were assessed by a standardized questionnaire and as a crude measure of possible exposure to helminths, IgG antibodies to Ascaris lumbricoides were measured. Results:, Exposure to nematodes, as determined by the levels of antibody to A. lumbricoides, was more frequent among farmers' children than non-farmers' children (39.8%vs 31.1%, P = 0.03). This positive serology was found to be significantly associated with high total IgE levels [odds ratio (OR) = 3.05, 95% confidence interval (CI) = 1.81,5.12] and eosinophilia (OR = 2.84, 95% CI = 1.66,4.84). However, no association between anti-nematode serology and the prevalences of asthma, wheeze, hay fever or atopy was found. A weak association for atopy was observed after adjustment for total IgE. Conclusion:, Immunoglobulin G antibodies to A. lumbricoides, as a crude measure of possible exposure to helminths, did not indicate any protective effect against allergic diseases in this population. Although farmers' children had increased antibody levels reactive to helminth parasites indicating exposure, this did not explain the protective effect of farming against atopic diseases. [source] Effect of endotoxin on opossum oesophageal motor functionNEUROGASTROENTEROLOGY & MOTILITY, Issue 3 2000H. Park Endotoxin induces nitric oxide (NO,) synthase and alters gastrointestinal functions. We explored the effect of lipopolysaccharide (LPS) on oesophageal motor function at 6, 12, 24, and 48 h. The effects of inhibiting inducible NO, synthase (iNOS) were studied 12 h after administration of LPS with/without aminoguanidine (AG). Oesophageal manometry was performed and tissue bath studies were performed with muscle strips from the oesophagus and lower oesophageal sphincter (LOS). Plasma nitrite/nitrate concentrations were determined. The amplitudes of peristaltic pressure waves, resting LOS pressure and the percentage LOS relaxations were diminished by LPS. AG attenuated the decrease in amplitude of oesophageal pressure waves, LOS pressure, and percentage relaxation of LOS brought about by LPS. LPS decreased electrical field stimulation (EFS)-induced relaxation of LOS muscle. AG attenuated this decrease in LOS relaxation. The off-response of transverse oesophageal muscle strips was decreased, and AG antagonized this effect. Plasma concentrations of nitrite/nitrate were increased. The increase in plasma nitrite/nitrate was attenuated by AG. These studies support the hypothesis that endotoxin modulates oesophageal motor function by increasing NO production and suggest that this results from the induction of iNOS. [source] Variation of dust endotoxin concentrations by location and time within homes of young childrenPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2010Dennis R. Ownby Ownby DR, Peterson EL, Williams LK, Zoratti EM, Wegienka GR, Woodcroft KJ, Joseph CLM, Johnson CC. Variation of dust endotoxin concentrations by location and time within homes of young children. Pediatr Allergy Immunol 2010: 21: 533,540. © 2010 John Wiley & Sons A/S Endotoxin may affect the development of allergic disease in childhood but little is known about endotoxin variation within homes. We sought to determine endotoxin concentration agreement within homes when five locations were each sampled twice 5 months apart. Endotoxin was measured using the recombinant Limulus factor C assay in dust samples from 585 homes of children enrolled in a prospective study and again in 335 homes 5 months later. The five locations sampled in each home were the child's bedroom floor, child's bed, mother's bedroom floor, mother's bed and living room floor. Concentrations of 4 allergens (Can f 1, Fel d 1, Der f 1 and Bla g 2) were also measured from the child's bedroom floor. In pair-wise comparisons, endotoxin concentrations in all locations within each home were significantly different from all other locations (p < 0.001) except for the child's and mother's bedroom floors (p = 0.272). Spearman correlations between endotoxin concentrations from the different locations were all statistically significant (p < 0.05) but of modest magnitude (r = 0.24,0.54). Similarly, correlations at each site over the 5 month observation interval were statistically significant but modest (r = 0.17,0.44). Pets and season of the year did not affect correlations, although correlations were lower if the floor was not carpeted. Endotoxin concentrations at all locations were minimally correlated with allergen concentrations in both negative and positive directions (r = ,0.12 to 0.12). We conclude that a single measurement of endotoxin from a home dust sample provides an imprecise estimate of dust endotoxin concentrations in other locations within the home and over a relatively short observation interval. [source] Endotoxin Level Measurement in Hemodialysis Biofilm Using "The Whole Blood Assay"ARTIFICIAL ORGANS, Issue 6 2005Karine Marion-Ferey Abstract:, Biofilms have been found on the inner surface of silicone tubing inside dialysis machines. Endotoxin releasing from those biofilms increases the bioincompatibility of dialysis liquids and leads to long-term inflammatory complications among dialysis patients. Endotoxin measurement is recommended for the control of dialysis liquids. This article describes the use of a new method, the Whole Blood Assay (WBA), for endotoxin quantification in dialysis biofilms. Biofilms were suspended in sterile water by scraping the tubing samples. Diluted blood samples from healthy donors were stimulated overnight with the contaminated suspension. Stimulated mononuclear cells released IL-1, in response to endotoxins. IL-1, level was then measured using an ultrasensitive ELISA method. We demonstrated a semilogarithmic model in which the optical densities measured after the ELISA assay increases linearly with the levels of endotoxin. This model allowed the determination of the amount of endotoxins in biofilm samples with a detection limit of 0.032 EU/mL. Most of the time, the amounts of endotoxin measured by the WBA were higher than those measured by the Limulus Amoebocyte Lysate (LAL) assay. This study suggested the presence of "endotoxin-like" compounds different from the lipopolysaccharides that are not detected by the LAL assay. We concluded that the LAL is necessary but insufficient to have a representative quantification of endotoxins that could be hazardous to patient health. [source] Inhibition of LPS-induced chemokine production in human lung endothelial cells by lipid conjugates anchored to the membraneBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2002G Ch Beck In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A2 (sPLA2) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA2 in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA2 inhibitors, specifically, the extracellular PLA2 inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-, and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-,B by LPS but not its activation by TNF-, or IL-1. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA2 activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA2. It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA2 inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA2 inhibitor LY311727. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation. British Journal of Pharmacology (2002) 135, 1665,1674; doi:10.1038/sj.bjp.0704618 [source] Determinants of endotoxin levels in living environments of farmers' children and their peers from rural areasCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2004M. Waser Summary Background Lower frequencies of asthma and hayfever have been observed in children with contact to livestock. At school age, the amount of endotoxin measured in the dust of children's mattresses is inversely related to the occurrence of atopic asthma, hayfever and atopic sensitization both in children from farming and non-farming households. Objective The aim of the present study was to investigate which home and lifestyle characteristics of farm and non-farm families contribute to endotoxin levels measured in different indoor home environments. Methods In the framework of the Allergy and Endotoxin (ALEX) Study, endotoxin was measured in dust samples from the living room floor and the child's mattress of 319 farmers' families and 493 non-farming families, and in settled dust from stables. Endotoxin content of all dust samples was determined by a kinetic Limulus assay (Limulus - Amebocyte -Lysate test). Information about the child's activities on farms, home characteristics and cleaning behaviours was obtained from parental questionnaires. Results Endotoxin levels in stables did not predict the amount of endotoxin measured in floors or mattresses. However, a dose-dependent association between the child's activity on the farm and indoor home endotoxin levels was observed, both in farm and non-farm children. In non-farm children pet keeping and the frequency of floor cleaning were additionally associated with endotoxin levels, whereas in farm children parental farm activities, study area, time since last cleaning, the mattress type as well as younger age of the children contributed to increased microbial exposure. Conclusion These results demonstrate that regular contact to farm animals increases indoor home endotoxin concentrations, both in farm and non-farm children, and might thus explain the protective effect of contact to livestock on atopic outcomes. To assess children's individual exposure to a microbial environment, measures of mattress dust exposure are needed as stable endotoxin concentrations were not associated with indoor home levels. [source] The role of allergic rhinitis in upper respiratory tract inflammatory diseasesCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2004Y. Kurono Summary The number of patients with allergic rhinitis (AR) is increasing. Furthermore, patients with otitis media with effusion (OME) and chronic sinusitis (CS) are frequently complicated with AR. These findings suggest that AR has an impact on the pathogenesis of both OME and CS. The direct and indirect influence of AR on OME and CS was investigated by clinical and experimental studies to clarify the mechanism by which type I allergic reaction is associated with OME and CS. Clinical findings of patients with OME or CS complicated with AR were analysed and compared with those of nonallergic subjects. Samples such as sinus effusions and middle ear effusions (MEE) were collected from the patients and infiltration of inflammatory cells and concentrations of inflammatory cytokines determined. In addition, previous reports discussing the relationship between AR and OME or CS are reviewed. Eosinophil infiltration and oedema were remarkable in paranasal sinus mucosa of patients with CS complicated with AR, suggesting the presence of type I allergic reaction in sinus mucosa. However, there was little evidence of eosinophils in sinus effusions. Endotoxin was frequently detected in sinus effusions of patients with CS having AR as well as suppurative CS. Hypoxia was also considered an important factor inducing sinus pathology. Eosinophils and IgE antibodies in MEE were not increased in OME patients with AR. Anti-allergic medicine was effective in OME patients complicated with AR and improvement of nasal symptoms significantly correlated with that of ear symptoms. AR might be directly and indirectly associated with the pathogenesis of OME and CS. [source] The Lung Is The Major Site That Produces Nitric Oxide To Induce Acute Pulmonary Oedema In Endotoxin ShockCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2001Ru Ping Lee SUMMARY 1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively). 2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects. 3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P < 0.05) EPE. In blood-perfused lungs, pretreatment with NOS inhibitors, such as N, -nitro- L -arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P < 0.05). 4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted. [source] Inflammatory pathways between placenta and foetusACTA PAEDIATRICA, Issue 1 2001Mikko Hallman Recent evidence indicates that intra-amniotic endotoxin (LPS) and interleukin-1 alpha (IL-1,) accelerate foetal lung maturity and protect from respiratory distress syndrome (RDS) more effectively than does antenatal glucocorticoid. Inflammatory cytokines promote development of chronic lung disease in the premature, acute RDS (ARDS) in children and adults. Systemic exposure to LPS or cytokines can result in generalized multiorgan damage. The abnormal host defence in the foetus and the premature newborn need to be considered in therapeutic interventions. [source] Intra-amniotic endotoxin accelerates lung maturation in fetal rabbitsACTA PAEDIATRICA, Issue 1 2001Kristina Bry The hypothesis that endotoxin in amniotic fluid accelerates fetal lung maturation was tested. On day 25 of gestation, LPS (5 ,g/fetus) was injected intra-amniotically into one uterine horn of eight New Zealand white rabbits, whereas the contralateral amniotic sacs were injected with saline vehicle. The fetuses were delivered 48 h after LPS administration and their lungs were studied. One dam went into premature labor prior to the 48 h time point and was excluded from the study. Mean white cell counts in amniotic fluid and bronchoalveolar lavage fluid from LPS-treated fetuses were increased 3.2-fold (p= 0.04) and 9.9-fold (p= 0.04), respectively. Fetal weights and lung weights were not affected by LPS. Surfactant protein SP-A and SP-B mRNA expressions in LPS-treated fetuses were increased 2.3-fold (p= 0.03) and 1.4-fold (p= 0.04), respectively. Static lung compliance was increased in animals treated with LPS (p= 0.001). Lungs from LPS-treated animals had better aeration than those of controls. Mean volume of inflation-fixed lungs of LPS-treated fetuses was 1.7 times greater than that of controls (p= 0.03). Conclusion: Intra-uterine exposure to LPS increases surfactant protein expression and improves lung stability and aeration in preterm animals. [source] Effects of repeated injections of fibroblast-stimulating lipopeptide-1 on fever, formation of cytokines, and on the responsiveness to endotoxin in guinea-pigsACTA PHYSIOLOGICA, Issue 1 2009A. Greis Abstract Aims:, We investigated, whether the Toll-like receptors (TLRs)-2/6-agonist fibroblast-stimulating lipopeptide-1 (FSL-1), like the TLR-4 agonist lipopolysaccharide (LPS), induces a state of tolerance. We further tested the influence of repeated pre-treatment with FSL-1 on the animals' responsiveness to LPS. Methods:, Abdominal temperature was recorded in unrestrained guinea-pigs with intra-abdominally implanted radiotransmitters. Circulating concentrations of tumour necrosis factor (TNF) and interleukin-6 (IL-6) were measured with specific bioassays. We tested the effects of intra-arterial (i.a.) or intraperitoneal (i.p.) injections of 100 ,g kg,1 FSL-1, repeated five times at intervals of 3 days. The animals' responses to i.a. or i.p. injections of 10 ,g kg,1 LPS were determined another 3 days later and compared to those of naïve guinea-pigs. Results:, The FSL-1-induced TNF peak was significantly attenuated starting with the third i.a. administration, while fever was unimpaired and the IL-6-peak just tended to decrease. Fever and IL-6 in response to i.a. injections of LPS were identical in both groups, while circulating TNF was higher in naïve compared to FSL-1 pre-treated animals. The effects of repeated i.p. injections of FSL-1 were more pronounced resulting in attenuation of fever as well as circulating TNF and IL-6, the strongest reduction observed after the third stimulation with FSL-1. Repeated i.p. pre-treatment with FSL-1 induced hyporesponsiveness to i.p. administration of LPS compared to naïve animals with regard to fever and especially with regard to LPS-induced formation of cytokines. Conclusions:, There is a development of tolerance to FSL-1 and cross-tolerance between FSL-1 and LPS depending on the route of administration of the respective TLR-2/6 and TLR-4 agonists. [source] Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteersACTA PHYSIOLOGICA, Issue 1 2009A. Soop Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source] Left ventricular mechanical dyssynchrony is load independent at rest and during endotoxaemia in a porcine modelACTA PHYSIOLOGICA, Issue 4 2009R. A'roch Abstract Aim:, In diseased or injured states, the left ventricle displays higher degrees of mechanical dyssynchrony. We aimed at assessing mechanical dyssynchrony ranges in health related to variation in load as well as during acute endotoxin-induced ventricular injury. Methods:, In 16 juvenile anaesthetized pigs, a five-segment conductance catheter was placed in the left ventricle as well as a balloon-tipped catheter in the inferior vena cava. Mechanical dyssynchrony during systole, including dyssynchrony time in per cent during systole and internal flow fraction during systole, were measured at rest and during controlled pre-load reduction sequences, as well as during 3 h of endotoxin infusion (0.25 ,g kg,1 h,1). Results:, Systolic dyssynchrony and internal flow fraction did not change during the course of acute beat-to-beat pre-load alteration. Endotoxin-produced acute pulmonary hypertension by left ventricular dyssynchrony measures was not changed during the early peak of pulmonary hypertension. Endotoxin ventricular injury led to progressive increases in systolic mechanical segmental dyssynchrony (7.9 ± 1.2,13.0 ± 1.3%) and ventricular systolic internal flow fraction (7.1 ± 2.4,16.6 ± 2.8%), respectively for baseline and then at hour 3. There was no localization of dyssynchrony changes to segment or region in the ventricular long axis during endotoxin infusion. Conclusion:, These results suggest that systolic mechanical dyssynchrony measures may be load independent in health and during acute global ventricular injury by endotoxin. More study is needed to validate ranges in health and disease for parameters of mechanical dyssynchrony. [source] Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pigACTA PHYSIOLOGICA, Issue 1 2002R. J. M. Middelveld ABSTRACT The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann,Whitney U -test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann,Whitney U -test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h. [source] Maternal behavior changes after immune challenge of neonates with developmental effects on adult social behaviorDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2003Kathryn E. Hood Abstract To examine whether maternal responsiveness during interactions with endotoxin-treated pups contributes to long-term effects on social development, neonatal mice were fostered on postnatal day 1 to dams from three selectively bred lines that differ in social behaviors. On day 5, neonates were administered saline or 0.5 mg/kg endotoxin (lipopolysaccharide, i.p.). Observations of undisturbed dams and litters on days 2, 4, 6, and 8 showed modest line differences in maternal behaviors. At the peak intensity of the transient illness induced by endotoxin (3 hr postinjection on day 5), dams increased licking and decreased time off-nest for endotoxin, but not saline-treated pups. As adults, fostered-reared males were observed in brief social interactions. Males exposed to endotoxin early in life showed changes in adult social behaviors that depended on foster dam line as well as individual differences in maternal responsiveness. Maternal responsiveness to stressed neonates can ameliorate the social,developmental effects of early illness. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 42: 17,34, 2003. [source] Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horsesEQUINE VETERINARY JOURNAL, Issue 3 2007J. N. MOORE Summary Reasons for performing study: Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis. Hypothesis: Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro. Methods: Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli O55:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined. Results: Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities. Conclusions: Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor). Potential relevance: Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses. [source] Evaluation of in vitro properties of di-tri-octahedral smectite on clostridial toxins and growthEQUINE VETERINARY JOURNAL, Issue 7 2003J. S. Weese Summary Reasons for performing study: Clostridial colitis and endotoxaemia of intestinal origin are significant causes of morbidity and mortality in horses. Intestinal adsorbents are available for treatment of these conditions; however, little information exists supporting their use. Objectives: To evaluate the ability of di-tri-octahedral smectite to bind to Clostridium difficile toxins A and B, C. perfringens enterotoxin and endotoxin, inhibit clostridial growth and the actions of metronidazole in vitro. Methods: Clostridium difficile toxins, C. perfringens enterotoxin and endotoxin were mixed with serial dilutions of di-tri-octahedral smectite, then tested for the presence of clostridial toxins or endotoxin using commercial tests. Serial dilutions of smectite were tested for the ability to inhibit growth of C. perfringens in culture broth, and to interfere with the effect of metronidazole on growth of C. perfringens in culture broth. Results: Clostridium difficile toxins A and B, and C. perfringens enterotoxin were completely bound at dilutions of 1:2 to 1:16. Partial binding of C. difficile toxins occurred at dilutions up to 1:256 while partial binding of C. perfringens enterotoxin occurred up to a dilution of 1:128. Greater than 99% binding of endotoxin occurred with dilutions 1:2 to 1:32. No inhibition of growth of C. difficile or C. perfringens was present at any dilution, and there was no effect on the action of metronidazole. Conclusions: Di-tri-octahedral smectite possesses the ability to bind C. difficile toxins A and B, C. perfringens enterotoxin and endotoxin in vivo while having no effect on bacterial growth or the action of metronidazole. Potential relevance: In vivo studies are required to determine whether di-tri-octahedral smectite might be a useful adjunctive treatment of clostridial colifis and endotoxaemia in horses. [source] The effects of local anaesthetic solution in the navicular bursa of horses with lameness caused by distal interphalangeal joint painEQUINE VETERINARY JOURNAL, Issue 5 2003JOHN SCHUMACHER Summary Reasons for performing study: Analgesia of the palmar digital (PD) nerves has been demonstrated to cause analgesia of the distal interphalangeal (DIP) joint as well as the sole. Because the PD nerves lie in close proximity to the navicular bursa, we suspected that that analgesia of the navicular bursa would anaesthetise the PD nerves, which would result in analgesia of the DIP joint. Objectives: To determine the response of horses with pain in the DIP joint to instillation of local anaesthetic solution into the navicular bursa. Methods: Lameness was induced in 6 horses by creating painful synovitis in the DIP joint of one forefoot by administering endotoxin into the joint. Horses were videorecorded while trotting, before and after induction of lameness, at three 10 min intervals after instilling 3.5 ml local anaesthetic solution into the navicular bursa and, finally, after instilling 6 ml solution into the DIP joint. Lameness scores were assigned by grading the videorecorded gaits subjectively. Results: At the 10 and 20 min observations, median lameness scores were not significantly different from those before administration of local anaesthetic solution into the navicular bursa (P,0.05), although lameness scores of 3 of 6 horses improved during this period, and the 20 min observation scores tended toward significance (P = 0.07). At the 30 min observation, and after analgesia of the DIP joint, median lameness scores were significantly improved (P,0.05). Conclusions: These results indicate that pain arising from the DIP joint can probably be excluded as a cause of lameness, when lameness is attenuated within 10 mins by analgesia of the navicular bursa. Potential relevance: Pain arising from the DIP joint cannot be excluded as a cause of lameness when lameness is attenuated after 20 mins after analgesia of the navicular bursa. [source] Unphosphorylated STAT3 modulates alpha7 nicotinic receptor signaling and cytokine production in sepsisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2010Geber Peña Abstract The role of STAT3 in infectious diseases remains undetermined, in part because unphosphorylated STAT3 has been considered an inactive protein. Here, we report that unphosphorylated STAT3 contributes to cholinergic anti-inflammation, prevents systemic inflammation, and improves survival in sepsis. Bacterial endotoxin induced STAT3 tyrosine phosphorylation in macrophages. Both alpha7 nicotinic receptor (alpha7nAChR) activation and inhibition of JAK2 blunt STAT3 phosphorylation. Inhibition of STAT3 phosphorylation mimicked the alpha7nAChR signaling, inhibiting NF-,B and cytokine production in macrophages. Transfection of macrophages with the dominant-negative mutant STAT3F, to prevent its tyrosine phosphorylation, reduced TNF production but did not prevent the alpha7nAChR signaling. However, inhibition of STAT3 protein expression enhanced cytokine production and abrogated alpha7nAChR signaling. Alpha7nAChR controls TNF production in macrophages through a mechanism that requires STAT3 protein expression, but not its tyrosine phosphorylation. In vivo, inhibition of STAT3 tyrosine phosphorylation by stattic prevented systemic inflammation and improved survival in experimental sepsis. Stattic also prevented the production of late mediators of sepsis and improved survival in established sepsis. These results reveal the immunological implications of tyrosine-unphosphorylated STAT3 in infectious diseases. [source] Effects of Endotoxin Exposure on Cationic Amino Acid Transporter Function in Ovine Peripheral Blood Mononuclear CellsEXPERIMENTAL PHYSIOLOGY, Issue 2 2003Megan F. Clark Rodent models of sepsis differ from clinical human disease in that humans make substantially less whole-body nitric oxide and have different cellular responses to endotoxin. Sheep, when exposed to endotoxin, behave in a manner more similar to humans. Many studies of rodent peripheral blood mononuclear cells (PBMCs) exposed to endotoxin demonstrate increased cationic amino acid transporter function (particularly through the y+ transporter) to supply arginine substrate to upregulated nitric oxide synthase. Whether this is true in sheep is not known. We have studied cationic amino acid transport in sheep PBMCs stimulated with endotoxin, using labelled lysine. PBMCs stimulated both in vitro and in vivo show an initial reduction in total and y+ lysine transport (after 1-2 h exposure to endotoxin): a previously undescribed effect of endotoxin. In in vitro activated cells, the reduction in y+ transport was prevented by the lipoxygenase inhibitor, nordihydroguaretic acid (NDGA), and the phospholipase inhibitor 4-bromophenacyl bromide (4-BPAB), but not cyclohexamide or a number of other inhibitors of intracellular second-messenger pathways. In contrast after 14 h incubation, the expected increase in total and y+ lysine transport was seen. The increase in y+ transport could be prevented by cyclohexamide, dexamethasone, ibuprofen, the protein kinase C inhibitor sphingosine, NDGA and 4-BPAB. These results suggest that in response to endotoxin exposure there is an initial decrease in y+ activity mediated by a lipoxygenase product, followed by a substantial increase in y+ activity mediated by the products of either cyclo-oxygenase or lipoxygenase. Cyclo-oxygenase and/or lipoxygenase inhibition might be useful in reducing arginine transport, and hence nitric oxide production, in these cells. [source] Neuroendocrine Function and Chronic Inflammatory StressEXPERIMENTAL PHYSIOLOGY, Issue 5 2002Michael Harbuz The factors regulating susceptibility and severity of autoimmune diseases are poorly understood. That neuroendocrine factors are critical modulators in this regard is self-evident. For example, there are major gender differences in susceptibility with women at greater risk than men of, for example, rheumatoid arthritis (RA) and multiple sclerosis (MS). The hypothalamo-pituitary-adrenal (HPA) axis has rightly attracted a considerable amount of attention. Of particular interest has been the hypothesis that susceptibility to autoimmune disease may be related to an impaired responsiveness of the HPA axis; that is, an inability to mount an appropriate cortisol response with which to down-regulate the immune system might allow the immune system to rampage unchecked and attack self. This hypothesis links regulation of the release from the adrenal gland of the potent anti-inflammatory glucocorticoids to the disease process. Endogenous glucocorticoids are crucial for the regulation of the severity of the disease process. The hypothesis proposing a link between a hyporesponsive HPA axis and susceptibility to disease is compelling. However, evidence from a number of sources has suggested that this may not be the entire story and alterations in the activity of the HPA axis have not been consistently observed in patients with RA. This review will concentrate on recent findings concerning the HPA axis in determining susceptibility to, and in regulating the severity of, inflammatory processes in autoimmune disease. These studies have revealed that a single exposure to endotoxin can confer protection to subsequent development of inflammation in an arthritis model in both neonatal and adult rats. Behavioural differences within a single population of rats are associated with differences in the plasma corticosterone responses to stress. However, relative hyporesponsiveness is not reflected by an increase in the severity of inflammation. In humans with RA the dexamethasone-corticotrophin-releasing factor (CRF) test has revealed two distinct sub-populations of patients. Studies in patients with MS have shown that this is not related to depression but rather to the severity of the disease. A better understanding of these complex neuroendocrine interactions may lead to novel clinical interventions. [source] Biophysical characterization of the interaction of high-density lipoprotein (HDL) with endotoxinsFEBS JOURNAL, Issue 23 2002Klaus Brandenburg The interaction of bacterial endotoxins [lipopolysaccharide (LPS) and the ,endotoxic principle' lipid A], with high-density lipoprotein (HDL) from serum was investigated with a variety of physical techniques and biological assays. HDL exhibited an increase in the gel to liquid crystalline phase transition temperature Tc and a rigidification of the acyl chains of the endotoxins as measured by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The functional groups of the endotoxins interacting with HDL are the phosphates and the diglucosamine backbone. The finding of phosphates as target groups is in accordance to measurements of the electrophoretic mobility showing that the zeta potential decreases from ,50 to ,60 mV to ,20 mV at binding saturation. The importance of the sugar backbone as further target structure is in accordance with the remaining negative potential and competition experiments with polymyxin B (PMB) and phase transition data of the system PMB/dephosphorylated LPS. Furthermore, endotoxin binding to HDL influences the secondary structure of the latter manifesting in a change from a mixed ,-helical/,-sheet structure to a predominantly ,-helical structure. The aggregate structure of the lipid A moiety of the endotoxins as determined by small-angle X-ray scattering shows a change of a unilamellar/inverted cubic into a multilamellar structure in the presence of HDL. Fluorescence resonance energy transfer data indicate an intercalation of pure HDL, and of [LPS],[HDL] complexes into phospholipid liposomes. Furthermore, HDL may enhance the lipopolysaccharide-binding protein-induced intercalation of LPS into phospholipid liposomes. Parallel to these observations, the LPS-induced cytokine production of human mononuclear cells and the reactivity in the Limulus test are strongly reduced by the addition of HDL. These data allow to develop a model of the [endotoxin]/[HDL] interaction. [source] | ||||||||||||||||||||||||||||||||||||||||||||||