interleukin-8 and Neonatal-Sepsis

Neonatal sepsis, a clinical disorder developed by bacterial blood stream infections (BSI) in neonates, is one of the serious global public health problems that must be addressed. More than one million of the estimated global newborn deaths per year are occurred due to severe infections. The genesis of the infection is divided into early-onset sepsis (EOS) and late-onset sepsis (LOS) of the disease. The clinical complications of neonatal sepsis may be associated with bronchopulmonary dysplasia, ductus arteriosus and necrotizing enterocolitis. The clinical diagnosis and treatment of neonatal sepsis is highly complicated. Over the past few years distinct biomarkers have been identified. Most widely used biomarkers are C-reactive protein, Procalcitonin (PCT) and Serum amyloid A (SAA). Until recently, many potential biomarkers including Cell Surface antigens and Bacterial surface antigens and genetic biomarkers are being investigated. Protein biomarkers, cytokines and chemokines are getting much interest for identification of neonatal sepsis infection.

Topics: Antigens, Bacterial; Antigens, Surface; Bacteria; Bacterial Infections; Bacterial Proteins; Biomarkers; C-Reactive Protein; Calcitonin; Chemokines; Cytokines; Genes, Bacterial; Genetic Markers; Humans; Interleukin-6; Interleukin-8; Meta-Analysis as Topic; Neonatal Sepsis; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha

Neonatal sepsis accounts for 0.97% of all disability-adjusted life years worldwide. Interleukin-6 has been used in sepsis diagnosis, but cut-off values are missing.. Neonates admitted to the neonatal wards with measurements of serum interleukin-6 born between September 2015 and September 2019 were retrospectively analysed. Mean serum interleukin-6 values of patients who never had increased laboratory parameters of infection nor died during their stay and mean interleukin-6 values on the day of blood sampling for a later positive culture in patients with culture-confirmed sepsis were analysed for each time period.. In all, 8.488 values in 1.695 neonates, including 752 very-preterm-infants and 701 very-low-birthweight infants, were analysed. The AUC for interleukin-6 was 0.84-0.91 in all neonates, 0.88-0.89 in very-preterm and 0.89-0.91 in very-low-birthweight infants. Using interleukin-6 cut-off values of 80 pg/ml on day of life 1, 40 pg/ml on day of life 2-7 and 30 pg/ml after day of life 7, a sensitivity of 75% and a specificity of 81% for culture-confirmed sepsis were achieved. In very-preterm infants, the corresponding values were 74% for sensitivity and 83% for specificity and in very-low-birthweight infants 74% and 86%, respectively.. Serum interleukin-6 has high accuracy for the detection of neonatal sepsis.. Serum interleukin-6 can be used with high accuracy to detect sepsis in neonates with the cut-off values of 80 pg/ml on day of life 1, 40 pg/ml on day of life 2-7 and 30 pg/ml after day of life 7. Serum interleukin-6 can be used with high accuracy to detect sepsis in neonates and very-preterm as well as very-low-birthweight infants. Interleukin-6 values display distinct cut-off values depending on the chronological age of the infant. Our article provides the first cut-off values for interleukin-6 in the first days of life in neonates.

Topics: Biomarkers; C-Reactive Protein; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Interleukin-8; Neonatal Sepsis; Retrospective Studies; Sensitivity and Specificity; Sepsis

Escherichia coli and Group B streptococci (GBS) are the main causes of neonatal early-onset sepsis (EOS). Despite antibiotic therapy, EOS is associated with high morbidity and mortality. Dual inhibition of complement C5 and the Toll-like receptor co-factor CD14 has in animal studies been a promising novel therapy for sepsis.. Whole blood was collected from the umbilical cord after caesarean section (n = 30). Blood was anti-coagulated with lepirudin. C5 inhibitor (eculizumab) and anti-CD14 was added 8 min prior to, or 15 and 30 min after adding E. coli or GBS. Total bacterial incubation time was 120 min (n = 16) and 240 min (n = 14). Cytokines and the terminal complement complex (TCC) were measured using multiplex technology and ELISA.. Dual inhibition significantly attenuated TCC formation by 25-79% when adding inhibitors with up to 30 min delay in both E. coli- and GBS-induced inflammation. TNF, IL-6 and IL-8 plasma concentration were significantly reduced by 28-87% in E. coli-induced inflammation when adding inhibitors with up to 30 min delay. The dual inhibition did not significantly reduce TNF, IL-6 and IL-8 plasma concentration in GBS-induced inflammation.. Dual inhibition of C5 and CD14 holds promise as a potential future treatment for severe neonatal EOS.. Neonatal sepsis can cause severe host inflammation with high morbidity and mortality, but there are still no effective adjunctive immunologic interventions available. Adding CD14 and complement C5 inhibitors up to 30 min after incubation of E. coli or Group B streptococci in a human umbilical cord blood model significantly reduced complement activation and cytokine release. Dual inhibition of C5 and CD14 is a potential future therapy to modulate systemic inflammation in severe cases of neonatal sepsis.

Topics: Animals; Cesarean Section; Complement C5; Cytokines; Escherichia coli; Female; Fetal Blood; Humans; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Neonatal Sepsis; Pregnancy; Sepsis

The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prognostic markers for late-onset neonatal sepsis.. This prospective study included 49 septic neonates and 17 controls. Cholesterol (CT), Triglyceride (TG), Very-Low-Density (VLDLc), Low-Density (LDLc), and High-Density Lipoproteins (HDLc) were measured at admission (D0) and on days 3, 7 and 10 to evaluate septic shock outcomes. Cytokines and monocytes were evaluated by flow cytometry.. Septic newborns showed higher IL-6 and IL-8 at D0 and CT levels on D7 and on D10, which also presented higher TG, VLDLc and non-HDL cholesterol concentrations than controls. The septic shock group (n = 22) revealed a higher number of male subjects, CRP, IL-6, IL-8 and IL-10 levels, while lower TG, HDLc, monocyte numbers and M/H ratio at admission compared to the non-shock group (n = 27). M/H ratio and non-HDL cholesterol on D0 were risk factors for septic shock (OR = 0.70, 0.49‒0.99; OR = 0.96, 0.92‒0.99, respectively). Decreasing levels from D0 to D3 of CT (OR = 0.96, 0.93‒0.99), VLDLc (OR = 0.91, 0.85‒0.98), and non-HDL cholesterol (OR = 0.92, 0.87‒0.98) were also predictors of septic shock.. Lower M/H ratios and non-HDL cholesterol at admission and decreasing levels of cholesterol, VLDLc and non-HDL cholesterol during a hospital stay are associated with the development of septic shock in newborns with late-onset neonatal sepsis.

Topics: Cholesterol; Cholesterol, HDL; Cytokines; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Lipoproteins; Male; Monocytes; Neonatal Sepsis; Prospective Studies; Sepsis; Shock, Septic; Triglycerides

Neonatal sepsis is common, lethal, and hard to diagnose. In combination with clinical findings and blood culture, biomarkers are crucial to make the correct diagnose. A Swedish national inquiry indicated that neonatologists were not quite satisfied with the available biomarkers. We assessed the kinetics of 15 biomarkers simultaneously: ferritin, fibrinogen, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, procalcitonin, resistin, serum amyloid A (SAA), tumor necrosis factor (TNF)-α, tissue plasminogen activator-3 and visfatin. The goal was to observe how quickly they rise in response to infection, and for how long they remain elevated. From a neonatal intensive care unit, newborns ≥28 weeks gestational age were recruited. Sixty-eight newborns were recruited to the study group (SG), and fifty-one to the control group (CG). The study group subjects were divided into three subgroups depending on clinical findings: confirmed sepsis (CSG), suspected sepsis (SSG) and no sepsis. CSG and SSG were also merged into an entire sepsis group (ESG) for sub-analysis. Blood samples were collected at three time-points; 0 h, 12-24 h and 48-72 h, in order to mimic a "clinical setting". At 0 h, visfatin was elevated in SSG compared to CG; G-CSF, IFN-γ, IL-1β, -8 and - 10 were elevated in SSG and ESG compared to CG, whereas IL-6 and SAA were elevated in all groups compared to CG. At 12-24 h, IL-8 was elevated in ESG compared to CG, visfatin was elevated in ESG and SSG compared to CG, and SAA was elevated in all three groups compared to CG. At 48-72 h, fibrinogen was elevated in ESG compared to CG, IFN-γ and IL-1β were elevated in SSG and ESG compared to CG, whereas IL-8 and SAA were elevated in all three groups compared to CG. A function of time-formula is introduced as a tool for theoretical prediction of biomarker levels at any time-point. We conclude that SAA has the most favorable kinetics regarding diagnosing neonatal sepsis, of the biomarkers studied. It is also readily available methodologically, making it a prime candidate for clinical use.

Topics: Biomarkers; C-Reactive Protein; Case-Control Studies; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Kinetics; Male; Neonatal Sepsis; Prospective Studies; Serum Amyloid A Protein

To study the association between interleukin-8 (IL-8) rs4073 polymorphisms and susceptibility to sepsis in full-term neonates through a prospective study.. A total of 50 neonates who were diagnosed with sepsis based on positive blood culture from January to December 2017 were enrolled as the sepsis group. Fifty neonates who had clinical symptoms and negative blood culture were enrolled as the clinical sepsis group. Fifty neonates without infection were enrolled as the control group. Sequencing was used to detect the polymorphisms of IL-8 rs4073. The three groups were compared in terms of the frequencies of genotypes and alleles. A multivariate logistic regression analysis was used to investigate the association of IL-8 rs4073 genotypes with sepsis in full-term neonates.. There were significant differences in the frequencies of genotypes and alleles at IL-8 rs4073 among the three groups (P<0.05). The logistic regression analysis showed that a low gestational age and TT genotype at IL-8 rs4073 were risk factors for the pathogenesis of sepsis in neonates (P<0.05).. The full-term neonates with TT genotype at IL-8 rs4073 may be susceptible to sepsis.

Topics: Case-Control Studies; Genetic Predisposition to Disease; Humans; Infant, Newborn; Interleukin-8; Neonatal Sepsis; Polymorphism, Single Nucleotide; Prospective Studies

Reducing the hazards of the early-onset neonatal sepsis (EONS) is a priority justifying the further investigation for potential biomarkers for its early diagnosis.. We aimed to investigate the diagnostic value of presepsin, procalcitonin, lactoferrin, interleukin (IL)-6, and IL-8 for the early diagnosis of EONS.. A prospective comparative study, including 30 cases with highly suspected EONS and 30 matched controls, was conducted. Besides the complete blood count and blood culture, C-reactive protein, procalcitonin, presepsin, IL-6, IL-8, and lactoferrin were measured at the admission and after 72 hours.. At the time of the admission, presepsin, procalcitonin, C-reactive protein, and IL-8 were significantly higher in the sepsis group. The levels of presepsin, procalcitonin, and IL-8 significantly decreased after 72 hours of the admission. Presepsin, procalcitonin, IL-8, and IL-6 showed a high diagnostic ability for sepsis at admission with area under the curve of 0.934, 0.798, 0.775, and 0.751, respectively. The cutoff values of presepsin, procalcitonin, IL-8, and IL-6 were 821 pg/mL, 2.3 ng/mL, 54 pg/mL, and 24 pg/mL, with a sensitivity of 88.9%, 72.2%, 83.3%, and 94.4% and specificity of 85.7%, 80.9%, 71.4%, and 52.4%, respectively. Lactoferrin had the lowest diagnostic ability with area under the curve of 0.558.. Presepsin was the most accurate biomarker followed by procalcitonin, IL-8, and IL-6 regarding the early diagnosis and management of EONS. The combination between these biomarkers is highly recommended.. Further studies are needed to investigate the diagnostic ability of the combination of these biomarkers.

Topics: Biomarkers; C-Reactive Protein; Case-Control Studies; Early Diagnosis; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Male; Neonatal Sepsis; Peptide Fragments; Procalcitonin; Prospective Studies; Sensitivity and Specificity

Early onset sepsis (EOS) remains a major cause of mortality and morbidity in neonates, and traditional clinical markers effective for adults are less effective in these patients. This study aimed to assess the value of individual plasma biomarkers as well as biomarker combinations for predicting EOS in neonates.. This prospective study included 151 neonates with suspected EOS. Plasma levels of interleukin (IL)-27, IL-6, IL-8, tumor necrosis factor (TNF)-α, heat shock protein (HSP) 70, macrophage inflammatory protein (MIP)-1α, MIP-1β, granzyme B, and matrix metalloproteinase (MMP)-8 were measured through multiplex cytokine profiling and assessed along with C-reactive protein (CRP) and procalcitonin (PCT). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive ability of biomarkers individually and in combination. Logistic regression model was constructed to identify independent predictors of EOS.. The proven sepsis and probable sepsis groups were combined to form the infected group (n = 68), and the possible sepsis and low-risk sepsis groups were combined to form the uninfected group (n = 83). The ROC area under the curve was 0.747 for IL-27 (P <0.01). In addition, IL-6, TNF-α, HSP 70, MMP-8, PCT, and CRP were significantly predictive of EOS, whereas IL-8, granzyme B, MIP-1α, and MIP-1β were not. Both IL-27 and PCT were identified as independent predictors of EOS in the multivariate model, and the combined use of these markers showed significantly increased predictive ability for EOS.. Our results indicate that elevated IL-27 strongly correlates with EOS and may provide additional diagnostic value along with PCT.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Chemokine CCL3; Chemokine CCL4; Female; Granzymes; HSP70 Heat-Shock Proteins; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Interleukins; Male; Matrix Metalloproteinase 8; Neonatal Sepsis; ROC Curve; Tumor Necrosis Factor-alpha

In spite of advances in neonatal care and the new generation of antibiotics, neonatal sepsis is still a major cause of morbidity and mortality. Early diagnosis of neonatal sepsis is difficult because clinical signs are non-specific. Thus, new biomarkers are still needed for diagnosis. Gelsolin is an actin-binding plasma protein. Furthermore, extracellular gelsolin binds lipopolysaccharide and lipoteichoic acid, which are major virulence factors of Gram-negative and Gram-positive bacteria. The result of this binding is the inhibition of gelsolin's F-actin depolymerizing activity. Thus, gelsolin inhibits the release of IL-8 from human neutrophils subjected to lipoteichoic acid, lipopolysaccharide and heat-inactivated bacteria treatment. Our hypothesis is that pGSN levels decrease in neonatal infants with sepsis and this decrease might be used as a reliable biological marker. Forty patients who were diagnosed with severe sepsis at a neonatal intensive care unit were enrolled in the sepsis group. Twenty patients who were followed for prematurity were enrolled in the control group. The pGSN level at the time of diagnosis in the sepsis group was 33.98±11.44μg/ml, which was significantly lower than that of control group (60.05±11.3μg/ml, P<0.001) and after treatment (53.38±31.26μg/ml, P=0.003). Area under ROC curve was 0.96 (p: 0.0001, 95% CI; 0.90-0.99). Sensitivity was 90.32 (95% CI; 74.2-97.8), specificity was 95 (95% CI; 75.1-99.2). Plasma gelsolin significantly decreased in septic patient and recovery of decreased gelsolin levels correlated with clinical improvement. Thus, plasma gelsolin may be a usable marker for severe sepsis.

Topics: Actins; Area Under Curve; Biomarkers; Female; Gelsolin; Humans; Infant, Newborn; Interleukin-8; Lipopolysaccharides; Male; Morbidity; Neonatal Sepsis; Neutrophils; Prospective Studies; ROC Curve; Sensitivity and Specificity; Sepsis; Teichoic Acids