Plasma Cytokine Levels In Patients Research Articles

Monocyte Metabolism and Function in Patients Undergoing Cardiac Surgery.

ObjectiveCardiopulmonary bypass (CPB) can lead to systemic inflammation, which is associated with higher morbidity. Therefore, we investigated the metabolism of isolated blood monocytes before and after CPB compared to healthy controls.MethodsIn this prospective, monocentric, observational study, we included 30 patients undergoing CPB and 20 controls. We isolated monocytes from heparinized blood and investigated their metabolism by using Seahorse technology before (t0), 4 h (t4), and 24 h (t24) after the start of the CPB. We also examined programmed cell death 1 ligand (PD-L1), PD-L2, V-domain Ig suppressor of T cell activation (VISTA), and human leukocyte antigen-DR isotype (HLA-DR) using fluorescence-activated cell sorting analysis. Additionally, we investigated plasma cytokine levels in patients without and after ex vivo stimulation.ResultsCPB-induced inflammatory responses are shown by significantly elevated plasma interleukin-6 levels in the CPB group compared to baseline and controls [t0: 0 ng/ml (95%CI 0-0 ng/ml); t4: 0.16 ng/ml (95%CI 0.1-0.197 ng/ml), p < 0.0001; t24: 0.11 ng/ml (95% CI 0.1-0.16 ng/ml), p < 0.0001, and controls: 0 ng/ml (95% CI 0-0 ng/ml)]. The cytokine release in the ex vivo stimulation is reduced for lipopolysaccharide stimulation at t4 [t0: 35.68 ng/ml (95% CI 22.17-46.57 ng/ml) vs. t4: 15.02 (95% CI 10.25-24.78 ng/ml), p < 0.0001]. Intracellular metabolism of monocytes after CPB showed a protracted shift to aerobic glycolysis [t0: 179.2 pmol/min (95% CI 138.0-205.1 pmol/min) vs. t24: 250.1 pmol/min (95% CI 94.8-300.2 pmol/min), p < 0.0001]. Additionally, we observed an altered metabolism in monocytes in patients undergoing cardiac surgery compared to controls even before any surgical procedure [t0: 179.2 pmol/min (95% CI 138.0-205.1) vs. controls 97.4 (95% CI 59.13-144.6 pmol/min), p = 0.0031].ConclusionAfter CPB, patients' monocytes show a shift in metabolism from oxidative phosphorylation to aerobic glycolysis, which is associated with energy-demanding and proinflammatory processes. This is the first study to show changes in monocyte immunometabolism in cardiac surgery. Monocytes of patients undergoing cardiac surgery were leaning toward aerobic glycolysis even before any surgical procedure was conducted. Leaving the question of the pathophysiological mechanisms for future studies to be investigated and paving the way for potential therapy approaches preventing inflammatory effects of CPB.

Gut microbiota and plasma cytokine levels in patients with attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood mental disorder with undetermined pathophysiological mechanisms. The gut microbiota and immunological dysfunction may influence brain functions and social behaviours. In the current study, we aimed to explore the correlation of gut microbiome imbalance and inflammation in the pathophysiology of ADHD. Forty-one children with ADHD and thirty-nine healthy-control (HC) individuals were recruited. Faecal samples from all participants were collected and submitted for 16 S rRNA V3–V4 amplicon microbiome sequencing analysis. The plasma levels of 10 cytokines, including TNF-α, IL-6, IL-1β, IL-2, IL-10, IL-13, IL-17A, IFN-α2, IFN-γ, and MCP-1, were determined using a custom-made sandwich enzyme-linked immunosorbent assay (ELISA) developed by Luminex Flowmetrix. There was no significant difference between the ADHD and HC groups in species diversity in the faeces, as determined with α-diversity and β-diversity analysis. In the ADHD group, three differentially abundant taxonomic clades at the genus level were observed, namely Agathobacter, Anaerostipes, and Lachnospiraceae. Top differentially abundant bacteria and representative biological pathways were identified in children with ADHD using linear discriminant analysis (LDA) effect size (LEfSe), and the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis, respectively. The plasma levels of TNF-α were significantly lower in children with ADHD than in HCs. Within the ADHD group, the levels of TNF-α were negatively correlated with ADHD symptoms and diversity of the gut microbiome. Our study provides new insights into the association between gut microbiome dysbiosis and immune dysregulation, which may contribute to the pathophysiology of ADHD.

Detection of cytokine storm in patients with achalasia using ELISA.

Esophageal achalasia is characterized by abnormal peristaltic movements of the esophageal body and impaired relaxation of the lower esophageal sphincter (LES). However, its etiology remains unknown. In our previous study, it was shown that in the LES of patients with achalasia, hsv1-miR-H1 was overexpressed, ATG16L1 expression was downregulated and interleukin (IL)-1β levels were upregulated. However, systemic features were not evaluated. Herein, the plasma cytokine levels in patients with achalasia were determined. Plasma was collected from patients at Nagasaki University Hospital between February 2013 and March 2016, both before and after peroral endoscopic myotomy (POEM). Cytokine analysis was performed using plasma collected from 10 healthy individuals (control group) and 12 patients with achalasia using the Bio-Plex Pro™ Human Cytokine 27-plex assay kit. The levels of IL-17, IL-1β, C-C motif chemokine ligand 2, IL-4, IL-5, IL-1ra, IL-7, IL-12, interferon-γ, IL-2, fibroblast growth factor-2, colony-stimulating factor (CSF)2 and CSF3 were significantly higher in patients with achalasia compared with the control subjects. However, the levels did not differ between plasma samples collected before and after POEM. Thus, the occurrence of a cytokine storm was confirmed in the patients with achalasia.

Влияние селективных блокаторов янус-киназ и фосфодиэстеразы 4-го типа на концентрацию цитокинов в коже и крови больных псориазом

Влияние селективных блокаторов янус-киназ и фосфодиэстеразы 4-го типа на концентрацию цитокинов в коже и крови больных псориазом

The cytokine system dysfunction in the acute period of ischemic stroke in dynamics of correction with cryopreserved cord blood serum

The changes of the cytokine system in the dynamics of treatment of 350 patients in the acute period of ischemic stroke by cryopreserved cord blood serum (CCBS) “CryocellCryocord” were studied. This revealed simultaneous strong activation of pro- and anti-infl ammatory cytokines in debut of the disease confirms their direct relevance to the early initiation of local inflammatory changes in response to acute ische mic brain tissue damage. Positive Dynamics of normalization of plasma cytokine levels in patients, who additionally received CCBS can testify about anti-inflammatory effect of CCBS. Key words: ischemia, cord blood, cytokine, inflammation, macrophage

Correlation of Aqueous, Vitreous, and Plasma Cytokine Levels in Patients With Proliferative Diabetic Retinopathy.

PurposeTo investigate the relationship between proangiogenic and inflammatory cytokines in concurrent vitreous, aqueous, and plasma samples from patients with proliferative diabetic retinopathy (PDR).MethodsVitreous, aqueous, and plasma samples were analyzed using multiplex immunoassay for 10 PDR-related cytokines (IL-6, IL-8, TNF-α, monocyte chemoattractant protein-1 [MCP-1], macrophage inflammatory protein-1β [MIP-1β], VEGF receptor 1 [Flt-1], placental growth factor [PlGF], VEGF-A, VEGF-C, VEGF-D). A total of 17 patients with PDR and 7 controls were included. The primary outcome was correlation of cytokines in vitreous, aqueous, and plasma. The secondary outcome was the comparison of cytokine levels in controls and diabetics with and without recent anti-VEGF injection.ResultsThe following factors were elevated in diabetics compared with controls: vitreous IL-6, IL-8, TNF-α, MCP-1, MIP-1β, PlGF, and VEGF-A; and aqueous IL-6, IL-8, PlGF, and VEGF-C (all P < 0.05). Vitreous and aqueous IL-8, PlGF, and VEGF-A were significantly correlated in patients with PDR (all P < 0.05). Plasma cytokines were not correlated with those in vitreous and aqueous (all P > 0.05). Vitreous and aqueous IL-6, IL-8, TNF-α, PlGF, and VEGF-A differed among controls and diabetics with and without recent anti-VEGF injection (all P < 0.05). In one-to-one comparisons, aqueous VEGF-A levels were lower in diabetic patients who had recent anti-VEGF injection compared with those who did not (P = 0.01).ConclusionsIn this proof-of-concept study, IL-8, VEGF-A, and PlGF demonstrated a strong correlation in vitreous and aqueous of patients with PDR. The aqueous may serve as a proxy for vitreous for some cytokines involved in PDR. Recent anti-VEGF injections decreased VEGF-A levels in aqueous, but did not significantly affect other cytokines, suggesting a role for other targeted therapies in PDR management.

Plasma cytokine levels in patients with chronic alcohol overconsumption: Relations to gut microbiota markers and clinical correlates.

Alcohol-related morbidity may involve changes in the gut microbiota and immune dysregulation. We have previously demonstrated alterations in gut microbiota composition and functions in patients with alcohol overconsumption, and now aimed to investigate possible associations between cytokine levels, gut microbiota, and clinical symptoms. We included hospital inpatients with a history of chronic alcohol overconsumption. For comparison, we included control patients with a low alcohol intake. Cytokine levels (TGF-β1, TNF-α, IL-10, IL-8, IL-6, IFN-γ, MCP-1, IL-1RA, IL-1β, and IL-17) were determined using a customized V-plex assay. We then examined associations of cytokine levels with the abundance of Proteobacteria and Faecalibacterium, percentage of the short-chain fatty acid butyrate, psychiatric symptoms (Hospital Anxiety and Depression Scale), and biochemical liver variables. We included 28 patients with alcohol overconsumption (79% men), and 25 control patients (72% men). Patients with alcohol overconsumption had higher levels of IL-6 (p=0.002), IFN-γ (p=0.018), and MCP-1 (p=0.006), and lower levels of TGF-β1 (p=0.017) compared with control patients. Inverse correlations were found between Proteobacteria abundance and TNF-α (Rs=-0.55, p=0.02) and IL-8 (Rs=-0.58, p=0.014), and between Faecalibacterium and MCP-1 levels (Rs=-0.56, p=0.02) in the control patients, but not in patients with alcohol overconsumption. Patients with alcohol overconsumption reported more psychiatric symptoms, and these symptoms were inversely correlated with IL-10 levels. There were positive correlations between several of the assessed cytokines and biochemical liver variables, and negative correlations between cytokine levels and albumin. Patients with alcohol overconsumption had a cytokine profile suggestive of increased systemic inflammatory activity, with higher levels of pro-inflammatory cytokines (IL-6, IFN-γ, and MCP-1) and lower levels of anti-inflammatory cytokines (TGF-β1). The findings may represent a link between alcohol use and alcohol-related morbidity.

Circulating cytokines predict severity of rheumatic heart disease

BackgroundRheumatic heart disease (RHD) is associated with inflammation that damages cardiac valves, often requiring surgical interventions. The underlying mechanisms involved in the disease progression are not completely understood. This study aimed to evaluate cytokine plasma levels in patients with RHD as possible markers of disease severity. Methods and resultsEighty-nine patients with RHD, age of 41 years ±11.5 years, were prospectively enrolled. RHD severity was defined as valve dysfunction that required invasive intervention, either valve repair or replacement. Peripheral blood samples were collected from all patients for cytokine measurements. The patients were followed up to look at adverse clinical events defined as either the need for valve intervention or death.At baseline, 64 (71.9%) patients had previously undergone valve intervention, whereas 25 patients had stable clinical presentation. Patients with severe RHD displayed higher levels of inflammatory cytokines than patients with stable disease. Cluster analysis showed segregation of severe and stable RHD based on IL-6/TNF-α and IL-6/IL-17A, respectively. IL-6 and TNF-α expression were positively correlated in severe but not in stable RHD patients.During a median follow-up of 23 months, 16 patients (18%) had an adverse outcome. IL-10 at baseline (HR 1.24, 95% CI 1.08–1.43, p = 0.003), and IL-4 (HR 1.12, 95% CI 1.01–1.24, p = 0.041) were predictors of events during the follow-up. ConclusionsHigh levels of cytokines are associated with severity of RHD. The co-regulated expression of IL-6 and TNF-α is associated with severe valve dysfunction, whereas high IL-10 and IL-4 levels predicted subsequently adverse outcome.

Distribution of circulating T follicular helper cell subsets is altered in immunoglobulin A vasculitis in children.

BackgroundImmunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Previously, we demonstrated that patients with IgAV show abnormal proliferation of cluster of differentiation (CD)4+C-X-C chemokine receptor type (CXCR)5+ follicular helper T (Tfh) cells. Here, we explored the status of Tfh cell subsets and plasma cytokine levels in patients with IgAV.MethodsCD4+CXCR5+CD45RA−, CD45RA-CXCR3+CCR6−, CD45RA−CXCR3−CCR6−, CD45RA−CXCR3−CCR6+, and CD45RA−CXCR3+CCR6+ Tfh cell fractions and plasma concentrations of interferon-γ, interleukin (IL)-4, and IL-17A were evaluated by flow cytometry and a flow cytometric bead array, respectively, in 30 patients with IgAV and 15 healthy controls (HCs).ResultsTfh2 and Tfh17 cell fractions were larger and the Tfh2+Tfh17/Tfh1 ratio and plasmaIL-4 and -17A levels were higher in patients with IgAV than in the HCs. Only Tfh1 cell counts were reduced in the abdominal subtype. The elevations in Tfh2 and Tfh17 cell counts and plasma IL-4 levels were abrogated by treatment. Tfh2 cell number was positively correlated with serum IgA and plasma IL-4 levels, but negatively correlated with the serum C4 concentration, while Tfh17 cell number was positively correlated with the serum IgA level and Tfh2 cell counts.ConclusionsAbnormally high numbers of Tfh2 and Tfh17 cells are linked to the occurrence and development of IgAV, but are not specific to the abdominal type. Only Tfh1 cells play a critical role in abdominal-type IgAV.

P.2.b.035 - Elevated cytokine plasma levels in patients with major depressive disorder

P.2.b.035 - Elevated cytokine plasma levels in patients with major depressive disorder

Dynamic Susceptibility Contrast Enhanced (DSC) MRI Perfusion and Plasma Cytokine Levels in Patients after Tonic-clonic Seizures.

BackgroundInflammatory events in brain parenchyma and glial tissue are involved in epileptogenesis. Blood concentration of cytokines is shown to be elevated after tonic-clonic seizures. As a result of inflammation, blood-brain barrier leakage occurs. This can be documented by imaging techniques, such is dynamic susceptibility contrast enhanced (DSC) MRI perfusion. Our aim was to check for postictal brain inflammation by studying DSC MRI perfusion and plasma level of cytokines. We looked for correlations between number and type of introducing seizures, postictal plasma level of cytokines and parameters of DSC MRI perfusion. Furthermore, we looked for correlation of those parameters and course of the disease over one year follow up.Patients and methodsWe prospectively enrolled 30 patients, 8–24 hours after single or repeated tonic-clonic seizures.Results25 of them had normal perfusion parameters, while 5 had hyperperfusion. Patients with hyperperfusion were tested again, 3 months later. Two of 5 had hyperperfusion also on control measurements. Number of index seizures negatively correlated with concentration of proinflammatory cytokines IL-10, IFN-ϒ and TNF-α in a whole cohort. In patients with hyperperfusion, there were significantly lower concentrations of antiinflammatory cytokine IL-4 and higher concentrations of proinflammatory TNF-a.ConclusionsLong lasting blood- brain barrier disruption may be crucial for epileptogenesis in selected patients.

Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

Acute kidney injury is associated with early cytokine changes after trauma

Acute kidney injury (AKI) occurs in 26% of trauma patients and is associated with increased mortality and risk for nosocomial infections (NCIs). We compared serial plasma cytokine levels in patients with posttraumatic AKI to determine whether the early cytokine changes are associated with the occurrence of AKI and NCI. We performed a secondary analysis of the Inflammation and the Host Response to Injury database to include adult blunt trauma patients who had available plasma proteomic analyses. AKI was defined by the RIFLE (Risk, Injury, Failure, Loss, and End-stage Kidney) classification, which requires a 50% increase in serum creatinine. The association among AKI, NCI, and plasma cytokines was analyzed using a mixed model analyses and logistic regression. Among 147 patients in the cohort, prevalence of NCI was 73% and 52% for patients with and without AKI, respectively. In mixed model analyses adjusted for clinical factors, AKI patients developed significant early increase in IL-1ra, IL-8, MCP1, and IL-6; early decrease in sTNFR2; and late decrease in IL-1ra, IL-4, and IL-6 concentrations, compared with patients without AKI and regardless of NCI. The change in cytokine pattern differed for sIL1R2, CXCL1, and MIP1β, depending on the occurrence of NCI. Patients with AKI and NCI had lower early and late sIL1R2 and higher early and late CXCL1 and MIP1β levels. Within the first 24 hours of injury, adding plasma levels of IL-1ra, IL-8, MCP1, IL-6, and sTNFR2 to clinical parameters of injury severity provided a predictive model for AKI superior to clinical model only (p < 0.001). AKI trauma patients exhibit simultaneous changes in proinflammatory and anti-inflammatory serial plasma cytokine levels. The predictive model for AKI that combines plasma cytokine levels with clinical data within 24 hours of injury requires further prospective validation in larger studies. Prognostic study, level III.

Differential Plasma Cytokine Levels in Patients with and without Chronic Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

AbstractAbstract 4476Chronic graft-versus-host disease (cGVHD) is a serious and frequent complication of allogeneic hematopoietic stem cell transplantation (HSCT). It is not known why some patients develop cGVHD and others do not, but identifying predictive biomarkers would facilitate the development of pre-emptive therapeutic strategies. Investigation into the pathophysiology of cGVHD has revealed different patterns of immune reconstitution in patients who develop cGVHD following HSCT. This suggests that the development of cGVHD occurs as a result of altered immune homeostasis and the inability to establish B and T cell tolerance. We prospectively examined 88 patients with hematologic malignancies following allogeneic HSCT at the Brigham and Woman’s Hospital/Dana-Farber Cancer Institute between the years 2004 and 2008 and measured plasma cytokines known to modulate effector T cell, regulatory T cell, and B cell homeostasis and function. Seventy-six patients (86%) received reduced intensity conditioning; 84 (95%) received filgrastim-mobilized peripheral blood stem cells. Median follow-up for all patients was 5 years (range 2.9 to 7.3 years). Fifty-nine percent developed cGVHD. Plasma samples were collected at 1, 3, 6, and 12 months after HSCT and multiplex Luminex bead assays were used to measure levels of the following cytokines: Interferon-γ, IL-2, IL-7, IL-1β, IL-12, TNFα, IL-4, IL-5, IL-6, IL-10, and GM-CSF. Cytokine levels in patients who developed cGVHD were compared to patients who did not develop cGVHD. Results are shown in figure 1. Significantly higher levels of IL-4, IL-6, IL-12, and IL-1β were observed at 1 and/or 3 months after transplantation in patients who subsequently developed cGVHD. IL-4 and IL-6 are characteristic of T-helper-2 (TH2) cellular and humoral immune responses previously associated with cGVHD and fibrogenesis. IL-12 and IL-1β have heterogeneous functions including stimulating interferon-γ and TNFα production, enhancing cytotoxic and helper T cells, and promotion of autoimmunity. IL-1α also stimulates IL-6 production and activates fibroblasts. Finally, GM-CSF was significantly elevated in patients who do not develop cGVHD at 1 year following HSCT (2.5 v 1.46 pg/mL, p=0.017). As shown in figure 1, we observed a general pattern for many cytokines, including IFNγ, IL-2, IL-4, IL-5, IL-6, and IL-1β, in which these cytokines are initially similar in both groups, or lower in patients without cGVHD, but gradually increase over time in patients who do not develop cGVHD. In contrast, cytokine levels remain stable in patients with cGVHD and are generally lower 1 year after transplantation in these patients. These late differences may reflect immune suppressive therapies as well as persistent abnormalities of immune homeostasis. Taken together, these results support the hypothesis that alterations in immune homeostasis early after allogeneic HSCT are significantly associated with the subsequent development of cGVHD. Manipulation of the cytokine environment early after HSCT can modulate immune homeostasis and may be of potential prophylactic value. Administration of homeostatic cytokines late after HSCT may also have therapeutic benefit. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Effect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis.

BackgroundSputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy.MethodsTwenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion.ResultsPlasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators.ConclusionsThese data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.

The Association Between BMI and Plasma Cytokine Levels in Patients With Acute Lung Injury

Obesity is associated with poor outcomes in many diseases, although recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting because obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in patients who are obese and critically ill or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI. We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor-alpha receptor 1, surfactant protein D [SP-D], soluble intracellular adhesion molecule, von Willebrand factor (vWF), protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1,409 participants in prior National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials. BMI was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFDs), organ failure-free days (OFDs), and mortality were investigated in regression models adjusting for confounders. In adjusted analyses, plasma IL-6 (P = .052), IL-8 (P = .001), and SP-D (P < .001) were inversely related to BMI, whereas vWF (P = .001) and WBC count (P = .042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFDs, or OFDs. Patients who are obese and have ALI have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in patients with ALI and a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of patients who are obese. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms.

Changes in natriuretic peptide and cytokine plasma levels in patients with heart failure, after treatment with high dose of furosemide plus hypertonic saline solution (HSS) and after a saline loading

Background and Aims Neurohormonal activation and inflammation characterizes heart failure, relates to outcome, and is a therapeutic target. The aim of this study was to evaluate the effects of high-dose furosemide plus small-volume hypertonic saline solutions (HSS) on natriuretic peptides and immuno-inflammatory marker levels and to analyze, after treatment, the response to acute saline loading. Methods and Results 120 patients with heart failure treated with high-dose furosemide + HSS ( Furosemide/HSS group) were matched with: 30 subjects with heart failure treated with high-dose furosemide ( furosemide group), 30 controls with asymptomatic left-ventricular dysfunction (ALVD) ( asymptomatic group) and 30 controls without heart failure or ALVD ( Healthy group). We evaluated plasma levels of natriuretic peptides and cytokine levels in baseline, after treatment and after acute saline load. After treatment with high-dose furosemide + HSS compared to treatment with furosemide alone we observed a significant lowering of ANP [96 (46.5–159.5) pg/ml vs 64 (21–150) pg/ml], BNP [215.5 (80.5–487) pg/ml vs 87 (66–141.5) pg/ml], TNF-α [389.5 (265–615.5) pg/ml vs 231.5 (156–373.5) pg/ml], IL-1β [8 (7–9) pg/ml vs 4 (3–7) pg/ml], IL-6 [5 (3–7.5) pg/ml vs 3 (2–4) pg/ml], plasma values and after an acute saline load, a lower percentage change of ANP (+18.6% vs +28.03% vs +25% vs +29%), BNP (+14.5% vs +29.2% vs +30% vs +29.6%) TNF-α (+10.8% vs +15.8% vs +17.8% vs +11.3%), IL-1β (+20% vs 34.4% vs 40% vs 34.4%) compared to control groups. Conclusions Treatment with HSS could be responsible for a stretching relief that could influence natriuretic and immuno-inflammatory markers.

Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: A randomized controlled trial*

The impact of continuous venovenous hemofiltration on sepsis-induced multiple organ failure severity is controversial. We sought to assess the effect of early application of hemofiltration on the degree of organ dysfunction and plasma cytokine levels in patients with severe sepsis or septic shock. Prospective, randomized, open, multicenter study setting, 12 French intensive care units. A total of 80 patients were enrolled within 24 hours of development of the first organ failure related to a new septic insult. Patients were randomized to group 1 (HF), who received hemofiltration (25 mL/kg/hr) for a 96-hour period, or group 2 (C) who were managed conventionally. The primary end point was the number, severity, and duration of organ failures during 14 days, as evaluated by the Sepsis-Related Organ Failure Assessment score, on an intention-to-treat analysis. Strict guidelines were provided to perform continuous hemofiltration under the same conditions and bearing the same objectives in all centers. Because of inclusion stagnation, the trial was discontinued after an interim analysis by which time 76 patients had been randomized. The number and severity of organ failures were significantly higher in the HF group (p < 0.05). No modifications in plasma cytokine levels could be detected. These data suggest that early application of standard continuous venovenous hemofiltration is deleterious in severe sepsis and septic shock. This study does not rule out an effect of high-volume hemofiltration (>35 mL/kg/hr) on the course of sepsis.

Aprotinin Reduces Cardiac Troponin I Release and Inhibits Apoptosis of Polymorphonuclear Cells During Off-Pump Coronary Artery Bypass Surgery

In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. A prospective randomized clinical trial. University hospital. Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor alpha; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (p = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery.

Present status and perspectives of bioartificial kidneys

Currently, hemodialysis is not adequate as a renal replacement therapy because it provides intermittent treatment and does not provide the metabolic function of renal tubules. The next generation of artificial kidney should replace intermittent hemodialysis with continuous hemofiltration and provide the full metabolic function of renal tubules. The current decade has witnessed the development of bioartificial kidneys using artificial membranes and renal tubular epithelial cells. Active transport and metabolic functions were confirmed in the confluent monolayers of tubular cells on artificial membranes. Bioartificial kidneys have succeeded in improving the prognosis of patients with multiple organ dysfunction, presumably by lowering plasma cytokine levels in patients. For successful treatment of chronic renal failure using bioartificial kidneys, it is necessary to overcome some technical hurdles such as improving the antithrombogenic properties of the surface of artificial membranes and prolonging the function of renal tubule cells on an artificial membrane. Transfection of functional protein genes into renal tubule cells enables bioartificial tubule devices to increase their transport capacity and metabolic functions such as digoxin secretion and water transport. The development of wearable roller pumps is also essential for the clinical application of a continuous treatment system.