Cytokine profile in severe Gram-positive and Gram-negative abdominal sepsis.
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ABSTRACT:
SUBMITTER: Surbatovic M
PROVIDER: S-EPMC4468818 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. The study included seventy-two critically ill patients admitted to the intensive care unit (ICU) of Nepean Hospital, Sydney, Australia. Of these, fifty-five patients were diagnosed to have sepsis, as confirmed by microbiological culture. The remaining seventeen patients did not have sepsis and were therefore used as controls. The study was approved by the hospital ethics committee and informed consent was obtained from all patients or their relatives. Patient Samples. Whole blood was taken from each patient on admission to ICU. Neutrophils were separated from whole blood using density-gradient separation with Ficoll-PaqueP P(Amersham). Subsequent neutrophil RNA extraction was performed using guanidinium thiocyanate (Ambion). Microarray Experiment. The neutrophil RNA was converted to cDNA, fluorescently labeled and hybridized to its complimentary sequences on the microarray (Invitrogen). The fluorescent signals on each micrroarray were captured using the GenePix 4000B laser scanner (Axon Instruments). Expression level of each gene was represented by the intensity of its fluorescent signal. Data Extraction. All signal intensity values were processed using background-subtraction method. Prior to analysis, all values were log-transformed and normalized by fitting a print-tip group Lowess curve. Normalization minimizes bias due to dye chemistry, signal intensity or location of a gene on the array. It ensures the detection of genes that are truly differentially expressed, instead of those caused by experimental artifacts or variation in the hybridization process. After normalization, genes that had more than 50% of data missing were removed. We then selected genes that had at least 80% of the data showing two-fold changes from the geneâs median values. After filtering, 1617 genes were available for further analysis.
2010-05-25 | E-GEOD-6535 | biostudies-arrayexpress
Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. Keywords: disease state analysis, gram-positive sepsis, gram-negative sepsis
2007-12-01 | GSE6535 | GEO
Project description:BackgroundThe host response to bacterial sepsis is reported to be nonspecific regardless of the causative pathogen. However, newer paradigms indicated that the host response of Gram-negative sepsis may be different from Gram-positive sepsis, and the difference has not been clearly clarified. The current study aimed to explore the difference by identifying the differential gene sets using the genome-wide technique.MethodsThe training dataset GSE6535 and the validation dataset GSE13015 were used for bioinformatics analysis. The distinct gene sets of sepsis with different infections were screened using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). The intersection gene sets based on the two algorithms were confirmed through Venn analysis. Finally, the common gene sets between GSE6535 and GSE13015 were determined by GSEA.ResultsTwo immunological gene sets in GSE6535 were identified based on GSVA, which could be used to discriminate sepsis caused by Gram-positive, Gram-negative, or mixed infection. A total of 19 gene sets were obtained in GSE6535 through Venn analysis based on GSVA and GSEA, which revealed the heterogeneity of Gram-negative and Gram-positive sepsis at the molecular level. The result was also verified by analysis of the validation set GSE13015, and 40 common differential gene sets were identified between dataset GSE13015 and dataset GSE6535 by GSEA.ConclusionsThe identified differential gene sets indicated that host response may differ dramatically depending on the inciting organism. The findings offer new insight to investigate the pathophysiology of bacterial sepsis.
| S-EPMC8863667 | biostudies-literature
Project description:Sepsis is an inflammatory response to pathogens (such as Gram‑positive and Gram‑negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram‑positive and Gram‑negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram‑positive samples and 25 Gram‑negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram‑negative and Gram‑negative samples using cluster software and the TreeView software. To analyze the correlation of samples at the gene level, a similarity network was constructed using Cytoscape software. Functional and pathway enrichment analyses were conducted for the DEGs using DAVID. Finally, stochastic perturbation was used to determine the significantly differential functions between Gram‑positive and Gram‑negative samples. A total of 340 and 485 DEGs were obtained in Gram‑positive and Gram‑negative samples, respectively. Hierarchical clustering revealed that there were significant differences between control and sepsis samples. In Gram‑positive and Gram‑negative samples, myeloid cell leukemia sequence 1 was associated with apoptosis and programmed cell death. Additionally, NADH:ubiquinone oxidoreductase subunit S4 was associated with mitochondrial respiratory chain complex I assembly. Stochastic perturbation analysis revealed that NADH:ubiquinone oxidoreductase subunit B2 (NDUFB2), NDUFB8 and ubiquinol‑cytochrome c reductase hinge protein (UQCRH) were associated with cellular respiration in Gram‑negative samples, whereas large tumor suppressor kinase 2 (LATS2) was associated with G1/S transition of the mitotic cell cycle in Gram‑positive samples. NDUFB2, NDUFB8 and UQCRH may be biomarkers for Gram‑negative sepsis, whereas LATS2 may be a biomarker for Gram‑positive sepsis. These findings may promote the therapies of sepsis caused by Gram‑positive and Gram‑negative bacteria.
| S-EPMC5548058 | biostudies-literature
Project description:Bacterial keratitis (BK) is an ocular disorder associated with poor visual prognosis. Quantification of the associated inflammatory response may provide insight into the pathogenesis of BK and guide treatment options. In this exploratory study, we evaluated 45 BK patients and 20 healthy controls by optical coherence tomography and pro-inflammatory tear cytokine analysis. The aim was to quantify the differential morphological and cytokine inflammatory response between Gram-negative and Gram-positive BK and to determine the diagnostic value of corneal thickness (CT) and infiltrate thickness (IT) in distinguishing Gram-ve BK in a clinical cohort. Greater CT and IT, at clinical presentation, were indicative of Gram-ve infection with values detected of ≥ 950 μm and ≥ 450 μm, respectively. Combination of these CT and IT values had a 100% sensitivity and 83.3% specificity as a diagnostic indicator of Gram-ve infection. Similarly, there were higher levels of IL-1β, IL-6 and IL-8 cytokines were quantified in keratitis caused by Gram-negative bacteria. Among the different tear cytokines analysed, a significant reduction after three days of treatment was detected for pro-inflammatory cytokines IL-1β, IL-2, IL-6, IL-8 and TNF-α, prior to starting with the administration of steroid drops. Overall, this study shows the potential value of serial OCT and tear cytokine measurements in the management of BK.
| S-EPMC7674500 | biostudies-literature
Project description:IntroductionPatients after major surgery are at high risk of developing sepsis, which is accompanied by elevated serum levels of C-reactive protein (CRP) and procalcitonin (PCT). This study aimed to examine the differences in serum biomarker levels concerning the causative agent of sepsis in surgical patients.Material and methodsA retrospective study was carried out in the surgical intensive care unit (ICU) and included 81 septic patients admitted from January 2019 to May 2022, who had positive blood cultures (BC). Serum levels of PCT, CRP, white blood cells (WBC) and platelet counts were recorded on the day of the positive BC and over the following 3 days.ResultsPatients with gram(-) sepsis had significantly higher PCT levels, and lower platelet count compared to patients with gram(+) sepsis. High PCT and low platelets levels in all measurements were a significant predictor of gram(-) isolate with the highest predictive value on the third day after BC sampling, with AUROC 0.821 (95% CI: 0.692-0.950), P = 0.001, and AUROC 0.676 (95% CI: 0.541-0.811), P = 0.02, respectively. In multivariate logistic regression, platelets the day after BC sampling and PCT on the third day made a significant contribution in distinguishing gam(+) from gram(-) BC. Age and high serum CRP levels were significant predictors of poor outcomes.ConclusionsPCT and platelets may be useful biomarkers for predicting the causative agent of sepsis in surgical patients.
| S-EPMC10801538 | biostudies-literature
Project description:The aim of the project is to identify the host response related to Gram positive (S. pyogenes) or Gram negative (E. coli) induced sepsis in a controlled sepsis model. Therefore a well defined baboon sepsis model, established at the Ludwig Boltzmann Institute for experimental and clinical traumatology of Vienna, is used. The overall goal of the project is to define differentially expressed or processed genes which give rise to diagnostic and therapeutic targets and consequently better monitoring and earlier onset of therapy.
2010-04-27 | E-MARS-14 | biostudies-arrayexpress
Project description:A series of imidazolium bromide salts (NIM-Br 1a, 1b and 1c) bearing different lengths of alkyl chains were synthesized and theirin vitro antibacterial activities were determined by measuring the minimum inhibitory concentration (MIC) values for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis. In addition, these imidazolium derivatives were also evaluated against biofilm produced by these bacterial strains. All compounds were found to be effective against Gram-positive and Gram-negative bacteria, and also more effective on the S. aureus biofilm production than the others.
| S-EPMC6812458 | biostudies-literature
Project description:The aim of the project is to identify the late (24h) host response related to Gram positive (S. pyogenes) or Gram negative (E. coli) induced sepsis in a controlled sepsis model 24 hours a. Therefore a well defined baboon sepsis model, established at the Ludwig Boltzmann Institute for experimental and clinical traumatology of Vienna, is used. The overall goal of the project is to define differentially expressed or processed genes which give rise to diagnostic and therapeutic targets and consequently better monitoring and earlier onset of therapy.
2010-04-27 | E-MARS-15 | biostudies-arrayexpress
Project description:BACKGROUNDElevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare with those observed in critically ill patients with acute respiratory distress syndrome (ARDS) or sepsis due to other causes.METHODSWe used a Luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTSFifteen hospitalized COVID-19 patients, 9 of whom were critically ill, were compared with critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1β, IL-1RA, IL-6, IL-8, IL-18, and TNF-α between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONLevels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDINGFunding was received from NHLBI K23 HL125663 (AJR); The Bill and Melinda Gates Foundation OPP1113682 (AJR and CAB); Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687 NIH/NIAID U19AI057229-16; Stanford Maternal Child Health Research Institute; and Chan Zuckerberg Biohub (CAB).
| S-EPMC7526438 | biostudies-literature