Molecular Characterization of the Acute Inflammatory Response to Infections with Gram-Negative versus Gram-Positive Bacteria

Feezor, Robert J.; Oberholzer, Caroline; Baker, Henry V.; Novick, Daniela; Rubinstein, Menachem; Moldawer, Lyle L.; Pribble, John P.; Souza, Sonia; Dinarello, Charles A.; Ertel, Wolfgang; Oberholzer, Andreas

doi:10.1128/iai.71.10.5803-5813.2003

Cited by 198 publications

(166 citation statements)

References 36 publications

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“…29 Our data also revealed that host immune response assessed by using gene expression patterns may be different in children infected with Gram-positive versus Gram-negative bacteria. This is in agreement with studies by Ramilo et al, 18 Feezor et al, 39 and Yu et al 40 In contrast, Tang et al 41 did not find significant differences in critically ill adults. Nevertheless, these data need to be interpreted with caution because of the limited number of children with Gram-negative sepsis.…”

Section: Discussionsupporting

confidence: 72%

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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BACKGROUND: Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences. METHODS: This was a prospective observational double-cohort study conducted in VLBW (<1500 g) infants with culture-positive bacterial sepsis and non-septic matched controls. Blood samples were collected as soon as clinical signs of sepsis were identified and before antibiotics were initiated. Total RNA was processed for genome-wide expression analysis using Affymetrix gene arrays. RESULTS: During a 19-month period, 17 septic VLBW infants and 19 matched controls were enrolled. First, a three-dimensional unsupervised principal component analysis based on the entire genome (28 000 transcripts) identified 3 clusters of patients based on gene expression patterns: Gram-positive sepsis, Gram-negative sepsis, and noninfected control infants. Furthermore, these groups were confirmed by using analysis of variance, which identified a transcriptional signature of 554 of genes. These genes had a significantly different expression among the groups. Of the 554 identified genes, 66 belonged to the tumor necrosis factor and 56 to cytokine signaling. The most significantly overexpressed pathways in septic neonates related with innate immune and inflammatory responses and were validated by real-time reverse transcription polymerase chain reaction. CONCLUSIONS: Our preliminary results suggest that genome-wide expression profiles discriminate septic from nonseptic VLBW infants early in the neonatal period. Further studies are needed to confirm these findings.

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Section: Discussionsupporting

confidence: 72%

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

et al. 2014

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“…Previous studies have noted differences in immune parameters that can be used to characterize the host response to diseases caused by different agents. The levels of IL-1␤, IL-6, and IL-18 are higher in the plasma of patients with sepsis induced by gram-positive bacteria than in patients with sepsis induced by gram-negative bacteria (19). Neisseria meningitidis induces more IL-10 but less IFN-␥ production than Streptococcus pneumoniae, while Staphylococcus aureus induced minimal secretion of both cytokines (4).…”

Section: Discussionmentioning

confidence: 96%

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Lukaszewski

Yates

Jackson

et al. 2008

Clin Vaccine Immunol

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Postoperative or posttraumatic sepsis remains one of the leading causes of morbidity and mortality in hospital populations, especially in populations in intensive care units (ICUs). Central to the successful control of sepsis-associated infections is the ability to rapidly diagnose and treat disease. The ability to identify sepsis patients before they show any symptoms would have major benefits for the health care of ICU patients. For this study, 92 ICU patients who had undergone procedures that increased the risk of developing sepsis were recruited upon admission. Blood samples were taken daily until either a clinical diagnosis of sepsis was made or until the patient was discharged from the ICU. In addition to standard clinical and laboratory parameter testing, the levels of expression of interleukin-1␤ (IL-1␤), IL-6, IL-8, and IL-10, tumor necrosis factor-␣, FasL, and CCL2 mRNA were also measured by real-time reverse transcriptase PCR. The results of the analysis of the data using a nonlinear technique (neural network analysis) demonstrated discernible differences prior to the onset of overt sepsis. Neural networks using cytokine and chemokine data were able to correctly predict patient outcomes in an average of 83.09% of patient cases between 4 and 1 days before clinical diagnosis with high sensitivity and selectivity (91.43% and 80.20%, respectively). The neural network also had a predictive accuracy of 94.55% when data from 22 healthy volunteers was analyzed in conjunction with the ICU patient data. Our observations from this pilot study indicate that it may be possible to predict the onset of sepsis in a mixed patient population by using a panel of just seven biomarkers.

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“…These results imply that serum inflammatory molecule levels alone were insufficient data for identifying bacterial species. As different species of bacteria have common characteristics (such as lipopolysaccharide on gram-negative bacteria), a similar pattern of inflammatory molecules were produced by innate immune system (32). However, in order to identify bacterial species on the basis of the pattern of serum molecule expression levels, the present findings suggest that the detection of more molecules is necessary.…”

Section: Discussionmentioning

confidence: 76%

Inflammatory molecules expression pattern for identifying pathogen species in febrile patient serum

Liu

Lin

et al. 2016

Experimental and Therapeutic Medicine

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Abstract.Inflammatory molecules, such as cytokines and chemokines, have been considered markers for bacterial or viral infection in serum of patients in numerous studies. The aim of the present study was to investigate whether we were able to identify the pathogen species through patterns of inflammatory molecules. A total of 132 patients with elevated body temperature (tympanic temperature, >38.3˚C) were recruited for this study. The concentrations of various inflammatory molecules in the patients' serum were evaluated using a cytometric bead array. Higher concentrations of interleukin (IL)-6 and IL-8 were detected in bacterial infection groups (patients with positive and negative blood cultures), as compared with the viral infection group. Viral infection (including influenza and dengue viral infections) was associated with higher concentrations of interferon-γ-inducible protein 10 (IP-10), as compared with the bacterial infection group. In addition, IL-8 levels in the gram-negative bacteria group were higher, as compared with the gram-positive bacteria group. However, IL-8 was insufficient for bacterial species identification. By contrast, dengue virus infection induced the highest serum level of IP-10 among all groups. In conclusion, detection of the patterns of inflammatory molecules may aid the subsequent management and treatment modalities in hospitals, although evaluation of these molecules alone may be insufficient for identifying the pathogen species.

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Molecular Characterization of the Acute Inflammatory Response to Infections with Gram-Negative versus Gram-Positive Bacteria

Cited by 198 publications

References 36 publications

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Inflammatory molecules expression pattern for identifying pathogen species in febrile patient serum

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