Plasma Inflammatory Mediators Research Articles

Investigating the spill-over hypothesis: Analysis of the association between local inflammatory markers in sputum and systemic inflammatory mediators in plasma

Exposure to air pollutants represents a risk factor not only for respiratory diseases and lung cancer, but also for cardiometabolic diseases. It has been hypothesised that local inflammation in the lung and systemic subclinical inflammation are linked by impaired lung function and the spill-over of proinflammatory factors from the lung into the circulation which could act as intermediaries between environmental exposures and disease risk. We wanted to investigate whether local and systemic inflammatory markers are associated, which would support the spill-over hypothesis.Sputum and plasma samples were obtained from 257 women of the German SALIA cohort. We performed immunoassays to measure multiple biomarkers of airway inflammation in sputum as well as cytokines, chemokines and soluble adhesion molecules in plasma. Correlations were calculated and adjusted for potentially confounding variables.Even though several significant associations were detected between inflammatory mediators in sputum and plasma, correlation coefficients were rather low ranging from r≥−0.20 to r≤0.20. Comparatively stronger associations were observed between nitrite, eosinophil cationic protein, leukotrienes C/D/E4 and interleukin-8 in sputum. Notably, correlations were positive with all proinflammatory biomarkers and interleukin-1 receptor antagonist in plasma, whereas negative correlations were observed with the anti-inflammatory adipokine adiponectin.In conclusion, local inflammation in the lung and systemic subclinical inflammation appear mainly independently regulated in elderly women from the general population. Although we found multiple significant correlations between inflammatory biomarkers in sputum and plasma, our results do not provide clear support for the spill-over hypothesis.

Inducible Protein-10, a Potential Driver of Neurally Controlled Interleukin-10 and Morbidity in Human Blunt Trauma*

Blunt trauma and traumatic spinal cord injury induce systemic inflammation that contributes to morbidity. Dysregulated neural control of systemic inflammation postinjury is likely exaggerated in patients with traumatic spinal cord injury. We used in silico methods to discern dynamic inflammatory networks that could distinguish systemic inflammation in traumatic spinal cord injury from blunt trauma. Retrospective study. Tertiary care institution. Twenty-one severely injured thoracocervical traumatic spinal cord injury patients and matched 21 severely injured blunt trauma patients without spinal cord injury. None. Serial blood samples were obtained from days 1 to 14 postinjury. Twenty-four plasma inflammatory mediators were quantified. Statistical significance between the two groups was determined by two-way analysis of variance. Dynamic Bayesian network inference was used to suggest dynamic connectivity and central inflammatory mediators. Circulating interleukin-10 was significantly elevated in thoracocervical traumatic spinal cord injury group versus non-spinal cord injury group, whereas interleukin-1β, soluble interleukin-2 receptor-α, interleukin-4, interleukin-5, interleukin-7, interleukin-13, interleukin-17, macrophage inflammatory protein 1α and 1β, granulocyte-macrophage colony-stimulating factor, and interferon-γ were significantly reduced in traumatic spinal cord injury group versus non-spinal cord injury group. Dynamic Bayesian network suggested that post-spinal cord injury interleukin-10 is driven by inducible protein-10, whereas monocyte chemotactic protein-1 was central in non-spinal cord injury dynamic networks. In a separate validation cohorts of 356 patients without spinal cord injury and 85 traumatic spinal cord injury patients, individuals with plasma inducible protein-10 levels more than or equal to 730 pg/mL had significantly prolonged hospital and ICU stay and days on mechanical ventilator versus patients with plasma inducible protein-10 level less than 730 pg/mL. This is the first study to compare the dynamic systemic inflammatory responses of traumatic spinal cord injury patients versus patients without spinal cord injury, suggesting a key role for inducible protein-10 in driving systemic interleukin-10 and morbidity and highlighting the potential utility of in silico tools to identify key inflammatory drivers.

Influence of feeding graded levels of canned sardines on the inflammatory markers and tissue fatty acid composition of Wistar rats.

Canned sardines are a ready-to-use fish product with excellent nutritional properties owing to its high n-3 long-chain PUFA content, mainly EPA (20 : 5n-3) and DHA (22 : 6n-3). The present study aimed to assess the effect of two dosages of canned sardines, recommended for the primary and secondary prevention of human CVD, on the inflammatory marker concentrations and fatty acid composition of erythrocytes and key metabolic tissues (liver, muscle, adipose tissue and brain) in the rat model. Wistar rats were fed a diet containing 11 % (w/w) of canned sardines (low-sardine (LS) diet) and a diet containing 22 % (w/w) of canned sardines (high-sardine (HS) diet) for 10 weeks. Daily food intake, weight gain, and organ and final body weights were not affected by the dietary treatments. The concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol decreased in both the LS and HS groups, while those of alanine aminotransferase and adiponectin increased. The concentrations of IL-1β increased only with the highest dosage of sardine. The dose-dependent influence of the graded levels of EPA+DHA was tissue specific. Compared with that of other tissues and erythrocytes, the fatty acid composition of the brain was less affected by the canned sardine-supplemented diets. In contrast, the retroperitoneal adipose tissue was highly responsive. The deposition ratios of EPA and DHA indicated that the LS diet was optimal for DHA deposition across the tissues, except in the retroperitoneal adipose tissue. Taken together, our findings indicate that a LS diet positively affects plasma lipid profiles and inflammatory mediators, whereas a HS diet has contradictory effects on IL-1β, which, in turn, is not associated with variations in the concentrations of other pro-inflammatory cytokines. This finding requires further investigation and pathophysiological understanding.

The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial

BackgroundInterleukin-1 (IL-1) is a key mediator of ischaemic brain injury induced by stroke and subarachnoid haemorrhage (SAH). IL-1 receptor antagonist (IL-1Ra) limits brain injury in experimental stroke and reduces plasma inflammatory mediators associated with poor outcome in ischaemic stroke patients. Intravenous (IV) IL-1Ra crosses the blood–brain barrier (BBB) in patients with SAH, to achieve cerebrospinal fluid (CSF) concentrations that are neuroprotective in rats.MethodsA small phase II, double-blind, randomised controlled study was carried out across two UK neurosurgical centres with the aim of recruiting 32 patients. Adult patients with aneurysmal SAH, requiring external ventricular drainage (EVD) within 72 hours of ictus, were eligible. Patients were randomised to receive IL-1Ra (500 mg bolus, then a 10 mg/kg/hr infusion for 24 hours) or placebo. Serial samples of CSF and plasma were taken and analysed for inflammatory mediators, with change in CSF IL-6 between 6 and 24 hours as the primary outcome measure.ResultsSix patients received IL-1Ra and seven received placebo. Concentrations of IL-6 in CSF and plasma were reduced by one standard deviation in the IL-1Ra group compared to the placebo group, between 6 and 24 hours, as predicted by the power calculation. This did not reach statistical significance (P = 0.08 and P = 0.06, respectively), since recruitment did not reach the target figure of 32. No adverse or serious adverse events reported were attributable to IL-1Ra.ConclusionsIL-1Ra appears safe in SAH patients. The concentration of IL-6 was lowered to the degree expected, in both CSF and plasma for patients treated with IL-1Ra.

Relationship between acid-base status and inflammation in the critically ill.

IntroductionThere is a complex interplay between changes in acid–base components and inflammation. This manuscript aims to explore associations between plasma cytokines and chemokines and acid–base status on admission to intensive care.MethodsWe conducted a prospective cohort study in a 13-bed ICU in a tertiary-care center in Brazil. 87 unselected patients admitted to the ICU during a 2-year period were included. We measured multiple inflammatory mediators in plasma using multiplex assays and evaluated the association between mediator concentrations and acid–base variables using a variety of statistical modeling approaches, including generalized linear models, multiadaptive regression splines and principal component analysis.ResultsWe found a positive association between strong ion gap (SIG) and plasma concentrations of interleukin (IL)6, 8, 10 and tumor necrosis factor (TNF); whereas albumin was negatively associated with IL6, IL7, IL8, IL10, TNF and interferon (IFN)α. Apparent strong ion difference (SIDa) was negatively associated with IL10 and IL17. A principal component analysis including SAPS 3 indicated that the association between acid–base components and inflammatory status was largely independent of illness severity, with both increased SIG and decreased SIDa (both drivers of acidosis) associated with increased inflammation.ConclusionAcid–base variables (especially increased SIG, decreased albumin and decreased SIDa) on admission to ICU are associated with immunological activation. These findings should encourage new research into the effects of acid–base status on inflammation.

Effect of early enteral nutrition with Bifico on levels of inflammatory mediators in plasma of patients with severe acute pancreatitis

Effect of early enteral nutrition with Bifico on levels of inflammatory mediators in plasma of patients with severe acute pancreatitis

Urinary Trypsin Inhibitor Ameliorates Seawater Immersion-Induced Intestinal Mucosa Injury via Antioxidation, Modulation of NF-κB Activity, and Its Related Cytokines in Rats with Open Abdominal Injury.

Objective. To investigate the role of oxidative stress, NF-κB activity, and its related cytokines in the pathogenesis of seawater immersion after open abdominal injury (SI-OAI) and whether UTI treatment can attenuate SI-OAI induced IMI. Methods. Wistar rats were randomly divided into three groups: C group, S group, and U group. The rats in C group only suffered from anesthesia and surgical operation, whereas the rats in S group and U group received caudal vein injection of normal saline without/with 50,000 U/kg body weight of UTI. The activities of TNF-α, IL-6, SOD, MDA, ROS, NF-κB, and IκB-β were monitored by ELISA, biochemical methods, EMSA, and Western blot, respectively. Results. The plasma inflammatory mediators and the contents of MDA, ROS, and NF-κB in intestine as well as the pathological scores in ileal mucosa were significantly increased in rats after SI-OAI, accompanied by a reduction in SOD activities and IκB-β levels. UTI treatment significantly attenuated intestinal histopathological changes with evidence of a decrease in all of the parameters, except for upregulation of the levels of SOD and IκB-β protein. Conclusion. UTI can attenuate SI-OAI induced IMI via inhibition of NF-κB activity, subsequently inhibiting the expression of inflammatory cytokines and by combating oxidative stress.

Systemic Inflammatory Response during Laparotomy.

Background. The aim of this study was to analyze the influence of laparotomy on the systemic inflammatory response in human patients suffering from secondary peritonitis. Study Design. A prospective study investigating the levels of white blood cells, C-reactive protein, platelets, interleukin-six, and tumor necrosis factor-alpha during laparotomy in five patients who suffered from secondary peritonitis. Six venous blood samples were collected perioperatively from each patient. The data were summarized by descriptive statistics and presented in a box plot. The hypothesis was that laparotomy increases the systemic inflammatory response, as has been described in animal models in previous studies. Results. The median age of the patients in this study was 84 years, the male to female ratio was 2 : 3, and the mortality rate was 80%. The most common cause of generalized peritonitis was ischemia of the colon. Analysis of the data showed no significant changes in the level of plasma inflammatory mediators during the surgical procedure, except for the platelet count which showed a significant decrease (P = 0.001). Conclusions. In contrast to experience with animal models, laparotomy in human patients with secondary peritonitis did not significantly increase the systemic inflammatory response. Furthermore, it contributed in significantly decreasing some of the systemic inflammatory mediators.

Effects of high volume hemofiltration on hemodynamics and oxygen metabolism at early stage of septic shock in piglet models

To observe the effects of hemofiltration at early stage of septic shock with different ultrafiltration doses, including hemodynamics, oxygen metabolism, inflammatory mediator in piglet models, and to evaluate the therapeutic effects of HVHF. The 18 healthy young piglets (Shanghai species) were divided randomly into three groups:control group (n = 6), conventional volume hemofiltration (CVVH) group [n = 6, ultrafiltration volume = 30 ml/(kg·h)] and high volume hemofiltration (HVHF) group [n = 6, ultrafiltration volume = 50 ml/(kg·h)], the animal model of septic shock was established by injection of lipopolysaccharide (LPS) (150 µg/kg) O111: B4. During the experiment, the following observations were carried out for all groups:1) Changes of hemodynamics [heart rate (HR), mean arterial pressure (MABP), cardiac output (CO), systemic vascular resistance index (SVRI), intrathoracic blood volume (ITBV)] and oxygen metabolism [oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction rate (O2ER) ] at the time of B0h, 0 h, 2 h, 4 h and 6 h.2) changes of TNF-α, IL-6, IL-10 in plasma at different time points (B0h, 0 h, 2 h, 4 h, 6 h). Significant difference in circulatory parameters, inflammatory mediators in plasma were found at B0h and 0 h among three groups; the CO in two treatment groups were higher than that in control group at 4 h, 6 h after model establishment (P < 0.05), and SVRI in HVHF groups were higher than that in other two groups at 4 h, 6 h after model was established (P < 0.05). The MABP in HVHF group [4 h (82 ± 17) mm Hg, 6 h (80 ± 12) mm Hg](1 mm Hg = 0.133 kPa) were higher than that in CVVH group at 4 h [(67 ± 12) mm Hg], 6 h [(69 ± 14) mm Hg] after model was established (P < 0.05). The levels of IL-6, IL-10, TNF-α in two treatment groups were lower than that in control group at 4 h and 6 h after model was established (P < 0.05), and the IL-6 [(281 ± 51) pg/ml], TNF-α [(67 ± 13) pg/ml] level in HVHF group was lower than that in CVVH group [IL-6(281 ± 51) pg/ml, TNF-α (67 ± 13) pg/ml] at 6 h (P < 0.05). The DO2 and VO2 in two treatment groups were higher than that in control group at 4 h, 6 h (P < 0.05), the O2ER in HVHF group were higher than that in CVVH group at 4 h (44% ± 3% vs. 33% ± 4%), 6 h (43% ± 5% vs. 31% ± 3%, P < 0.05). High volume hemofiltration (HVHF) at early stage of septic shock piglet models was more effective in improving hemodynamics, oxygen metabolism than conventional CVVH. And HVHF eliminated blood inflammatory mediators more effectively than conventional CVVH.

α1-Antitrypsin inhibits ischemia reperfusion-induced lung injury by reducing inflammatory response and cell death

Pulmonary ischemia-reperfusion (IR)-induced lung injury is a severe complication that increases the likelihood of primary graft dysfunction and early death after lung transplantation. Inflammatory cytokine release and cell death play a critical role in the development of IR-induced lung injury. α1-Antitrypsin (A1AT) is a protease inhibitor clinically used for the treatment of A1AT-deficiency emphysema. On the basis of a literature review, we hypothesize that A1AT may have the potential to reduce IR-induced lung injury through its anti-inflammatory and anti-apoptotic effects. A human pulmonary cell culture model was used to simulate IR processes in lung transplantation. Effects of A1AT on cell death and cytokine production were examined. A rat pulmonary IR model, in which the left pulmonary hilum was clamped for 90 minutes, followed by reperfusion for 2 hours, was used to determine the effects of A1AT on acute lung injury, function, cell death, and inflammatory response. A1AT significantly inhibited cell death and inflammatory cytokine release dose-dependently in vitro and significantly improved lung oxygenation and lung mechanics and reduced pulmonary edema in vivo. Moreover, A1AT inhibited neutrophil infiltration in the lung and reduced cell death and significantly reduced IR-induced inflammatory mediators in plasma, including interleukin (IL)-1α, IL-4, IL-12p70, monocyte chemotactic protein 1, and tumor necrosis factor-α. Considering its current clinical use, our findings indicate that administration of A1AT may be an effective and safe therapy for the treatment of IR injury in human lung transplantation.

Do High Levels of n-3 Polyunsaturated Fatty Acids in Cell Membranes Increase the Risk of Postoperative Atrial Fibrillation?

Objectives: Postoperative atrial fibrillation (POAF) has been associated with an inflammatory response to the surgical procedure. n-3 long-chain polyunsaturated fatty acids (LC-PUFA) have been proposed for the prevention of POAF. We investigated the relationship between the plasma concentration of inflammatory mediators, levels of n-3 LC-PUFA in red blood cell (RBC) membrane lipids, and the risk of POAF after coronary artery bypass grafting (CABG). Methods: A total of 125 patients who underwent CABG were studied. Inflammatory mediators in plasma and the content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in RBC membranes were assessed. Results: Sixty-two patients (49.6%) developed POAF. The POAF group had higher RBC levels of total n-3 LC-PUFA and DHA than did patients remaining in sinus rhythm (p < 0.05). Of the inflammatory mediators, only postoperative interleukin-6 levels differed, being higher in the POAF group (p < 0.05). Inflammatory mediators were not independent predictors of POAF by multivariable logistic regression analysis. Higher levels of DHA and total n-3 LC-PUFA in RBC membranes, measured immediately prior to CABG and on postoperative day 3, were linearly associated with an increased risk of POAF (p < 0.05). Conclusions: Our findings suggest that inflammatory mediators are not associated with the occurrence of POAF. Interestingly, high n-3 LC-PUFA levels in RBC membranes appear to increase the risk of POAF.

Mild obesity reduces survival and adiponectin sensitivity in endotoxemic rats

BackgroundRecent meta-analyses have reported that critically ill patients with morbid obesity (body mass index >40 kg/m2) have poor outcomes, but the effects and mechanisms of action of mild obesity are still unclear. The purpose of this study was to evaluate the effect of mild obesity using a lard-based, high-fat diet (HFD) on pathologic conditions and the mechanisms of adiponectin action in endotoxemic rats. Materials and methodsMale Wistar rats underwent HFD feeding for 4 wk and were killed at 0, 1.5, and 6 h after lipopolysaccharide (LPS) injection. Plasma levels of adiponectin, nitric oxide, and interleukin 6; messenger RNA expression of adiponectin receptors (AdipoR1 and AdipoR2) in the liver and the skeletal muscle; blood biochemical test results; and histology of the liver were analyzed. ResultsHFD-fed rats had a lower survival rate (12.8% versus 85.2%) and lower plasma adiponectin levels after LPS injection (P < 0.01). Messenger RNA expression of adiponectin receptors in the liver, but not the skeletal muscle, also decreased in HFD-fed rats (P < 0.05). Tissue injury and oxidative stress in the liver and plasma inflammatory mediator levels increased, and worsened lipid metabolism abnormalities were noted. The findings indicated that HFD decreased the sensitivity of adiponectin and was associated with an increase in oxidative stress and inflammation, which finally resulted in worsened liver injury and poor survival rate after LPS injection. ConclusionsShort-term, HFD-induced, mild obesity is harmful to the septic host, reduces adiponectin sensitivity, and could be the cause of worsening pathologic conditions.

Serum Protein Fraction in Mature Horses and Relationship With Metabolic and Hematological Parameters

This study was conducted to determine the effect of age on serum protein fractions and their relationship with metabolic and hematological profiles in mature horses. Twenty-five mature Italian Saddle horses (mean age 13.6 ± 4.8 years) fed the same diet (grass hay and concentrate) were stratified according to age as first maturity, M1 (≤10 years old); second maturity, M2 (>10 and <15 years old); and old, O (>15 years), to be monitored every 28 days for a continuous period of 140 days. Horses in group O had higher plasma protein and thiol concentrations and white blood cell and neutrophil counts than the other two groups. Serum α2-globulin concentrations were positively correlated with total plasma cholesterol (r = 0.514; P < .001), alkaline phosphatase (r = 0.430; P < .001), aspartate aminotransferase (r = 0.339; P < .001), ceruloplasmin (r = 0.321; P < .001), glutamic pyruvate transaminase (r = 0.444; P < .001), reactive oxygen metabolites (r = 0.426; P < .001), and blood neutrophil counts (r = 0.344; P < .01), and negatively with plasma bilirubin (r = −0.522; P < .001) and creatinine (r = −0.400; P < .001). These results suggest differences in hematological and metabolic profile in Italian Saddle horses after 15 years of age, resulting mainly from changes in plasma proteins and inflammatory mediators. The α2-globulins fraction seems a quick but reliable marker of an inflammatory situation that, successively, should be better investigated with specific metabolites or enzymes.

The effects of natural and modified clinoptilolite on intestinal barrier function and immune response to LPS in broiler chickens

The protection of intestinal barrier function and the anti-inflammatory effects of natural clinoptilolite (NCLI) and modified clinoptilolite (MCLI) were investigated in broilers that were repeatedly challenged with lipopolysaccharide (LPS). A total of 288 1-d-old broiler chicks were divided equally into three treatment groups: control, NCLI-treated (2%) and MCLI-treated (2%). Half of the birds from each treatment group were challenged with 0.9% NaCl solution or LPS (250μg/kg body weight, administered orally) at 16, 18 and 21d of age. The results indicated that, prior to LPS challenge, the diet had no effect on bird growth performance (P>0.05). The oral administration of LPS was also not associated with any significant changes in poultry performance (P>0.05). In LPS-challenged birds that were pretreated with NCLI (2%) or MCLI (2%), the LPS-induced increases in the plasma and intestinal mucosa concentrations of TNF-α, IL-1β, IL-2, IL-6, IL-4 and IL-10 were dramatically attenuated. Additionally, significant decreases in the plasma d-lactic acid and diamine oxidase (DAO) levels were found in birds that were pretreated with NCLI or MCLI. Furthermore, both NCLI and MCLI reduced the sICAM-1 concentration in the intestinal mucosa. In conclusion, NCLI and MCLI are able to prevent the LPS-induced intestinal mucosa damage and inflammatory response in vivo. These beneficial effects suggest that NCLI and MCLI act as anti-inflammatory agents in part by inhibiting neutrophil infiltration and hyperactivation and by suppressing the secretion of various plasma and intestinal mucosa inflammatory mediators.

Partial Depletion of Regulatory T Cells Does Not Influence the Inflammation Caused by High Dose Hemi-Body Irradiation

There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61) was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI). The blood, spleen, mesenteric lymph nodes (mLNs) and inguinal lymph nodes (iLNs) were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4+ T cells, CD8+ T cells, Treg cells, B cells, NK cells, NK1.1+ T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%). Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting.

Assessment of the inflammatory effect of low-dose oxygen in mechanically ventilated patients

Although low doses of oxygen (FiO2 <0.50) are considered nontoxic, recent studies have shown that even lower doses increase pulmonary inflammatory mediators. We aimed to evaluate the acute effects of reducing FiO2 on pulmonary inflammation in mechanically ventilated patients without respiratory failure. This study was a prospective, single-center crossover study in a medical/surgical intensive care unit at a university hospital. Hemodynamically stable patients under mechanical ventilation for >24 h without severe respiratory failure (PaO2/FiO2 >250). A basal FiO2 of 0.40 was reduced to 0.21 provided SpO2 remained higher than 90 %. Patients who could not tolerate the reduction in FiO2 to 0.21 were excluded. We screened 40 patients, but only 28 (70 %) tolerated FiO2 0.21. We measured common clinical variables and inflammatory mediators in plasma and in exhaled breath condensate (EBC) at the end of three 4-h periods: (1) basal (FiO2 0.40), (2) after FiO2 reduction to 0.21, and (3) after returning FiO2 0.40. We used one-way ANOVA for repeated measurements with FiO2 as the grouping variable. Median values of inflammatory mediators in EBC showed nonsignificant changes among the three periods: NO2 + NO3 17.1, 14.1 and 11.0 μmol/L (p = 0.2), and 8-isoprostane 4.4, 8.2 and 5.3 pg/ml (p = 0.6) for the three periods, respectively. Plasma levels also showed nonsignificant changes during the period of the study: NO2 + NO3 12.6, 16.3 and 15.0 μmol/L (p = 0.9), TNFα 13.5, 18.0 and 14.5 pg/ml (p = 0.8), IL-4 12.9, 18.7 and 23.9 pg/ml (p = 0.1), IL-6 50.9, 35.1 and 28.3 pg/ml (p = 0.6), and IL-10 15.2, 22.2 and 22.2 pg/ml (p = 0.7) for the three periods, respectively. FiO2 0.40 in mechanically ventilated patients without severe respiratory failure did not increase systemic or pulmonary inflammation.

Elevated neutrophil elastase and acrolein-protein adducts are associated with W256 regression

The involvement of granulocytes in immune response against cancer is not well understood. Depending on the cytokine milieu in which they act and on their oxidative burst, granulocytes may play either an inhibitory or stimulatory role in tumour growth. Unsaturated fatty acids, essential components of cellular membranes and storage lipids, are susceptible to granulocyte-derived reactive oxygen species (ROS). ROS can induce lipid peroxidation (LPO) resulting in the destruction of biomembranes. Thus, murine W256 tumour progressing and tumour regressing animal models were used to study the involvement of plasma inflammatory mediators and oxidative burst of circulating granulocytes in malignant destruction and detrimental tumour growth. The involvement of LPO-derived aldehydes (i.e. acrolein, 4-hydroxy-2-nonenal and malondialdehyde) and myeloperoxidase (MPO) appearance in the granulocyte anti-cancer response were further evaluated. The results obtained revealed a significant increase in neutrophil elastase in animals with regressing tumour. Furthermore, the presence of MPO in tumour microenvironment was accompanied by the formation of acrolein only 5 h after tumour transplantation and its presence increased during tumour regression. Later, at an early stage of tumour regression, the presence of other LPO-derived aldehydes were also observed. The results obtained suggest that elevated neutrophil elastase and initiation of LPO may play an important role in the tumour development leading to tumour regression.

CALCIUM ANTAGONIST COMBINED WITH STATIN THERAPY ON PLASMA INFLAMMATORY MEDIATORS IN PATIENTS WITH HYPERTENSION AND CAROTID ATHEROSCLEROSIS

ObjectivesTo investigate the effect of calcium antagonists (CCB) and statins on carotid plaques and plasma inflammatory mediators, so as to learn the possible mechanism of their anti-atherogenic effect.MethodsThis is a...

Fingerprinting of the TLR4-induced acute inflammatory response

Intensive scientific efforts in the past decades have helped shed light into the pathogenesis of endotoxin-induced inflammation. We have used multiplexing bead-based assays to characterize the responses in two models of in vivo LPS challenge. C57BL/6 mice were either injected intraperitoneally (endotoxemia) or intratracheally (acute lung injury; ALI) with lipopolysaccharide (LPS). The time courses (1h–24h) of the following 20 inflammatory mediators in plasma or broncho-alveolar lavages were simultaneously analyzed: IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-12(p40), IL-13, Eotaxin (CCL11), G-CSF, GM-CSF, IFN-γ, KC (CXCL1), MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5) and TNF-α. While significant inductions of all mediators were found, substantial differences in their absolute concentrations, time points of maximal concentrations and clearances were observed. There were also notable variations in the patterns of several cytokines/chemokines when samples from endotoxemia and LPS-ALI were compared. These data may be helpful in defining analytic strategies including selection of optimal time points for studying the host immune response to endotoxin.

The effects of zero-balance ultrafiltration on postoperative recovery after cardiopulmonary bypass: a meta-analysis of randomized controlled trials

Considered as a significant ultrafiltration technology during cardiopulmonary bypass (CPB), zero-balance ultrafiltration (Z-BUF) has always received controversial support regarding its effectiveness in reducing inflammatory mediators in plasma. Therefore, we conducted a meta-analysis to evaluate the clinical effect of Z-BUF through screening all relevant published randomized controlled trials (RCTs). A comprehensive search was conducted to screen all RCTs of Z-BUF. Three trained investigators searched databases, including PubMed, Embase, the Cochrane Library, Google scholar, and Chinese literature databases (CNKI, WanFang, WeiPu). RCTs that compared Z-BUF with non-ultrafiltration were included. We focused on clinical outcomes such as length of stay in ICU, duration of ventilation, hospital stay, total amount of chest tube drainage and mortality. Finally, a total of 7 studies containing appropriate criteria were divided into an adult group and a pediatric group. A random effects model was used to calculate weighted mean difference with 95% confidence intervals. In the adult group, the benefits of Z-BUF in duration of ventilation (WMD=-2.77, 95% CI = [-6.26, 0.72], I(2)=71%, p=0.12) and the length of ICU stay (WMD=-4.13, 95% CI = [-10.09, 1.84], I(2)=77%, Z=1.36, p=0.17) were not apparent, with significant heterogeneity existing in the statistical results. The rest of the clinical parameters could not be evaluated due to insufficient data. In the pediatric group, combined analysis showed Z-BUF could reduce the duration of mechanical ventilation (WMD=3.07; 95%CI= [-7.56, -3.46], I(2)=17%, p=0.27). The advantage of Z-BUF was not observed in other clinical outcomes. The benefits of Z-BUF were not apparent, according to the report. Further studies involving combined ultrafiltration are expected to provide improved ultrafiltration during CPB.