Predictive Value of Soluble Immunological Mediators in Neonatal Infection

Edgar, J. D. M.; Wilson, D. C.; McMillan, S A; Crockard, A.D.; Halliday, M. I.; Gardiner, Keith; Rowlands, B. J.; Halliday, Henry L.; McNeill, T. A.

doi:10.1042/cs0870165

Cited by 48 publications

(45 citation statements)

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“…Previous studies on the diagnostic value of plasma IL-8 in the prediction of EOBI reported this cytokine to be more sensitive but less specific than CRP at the onset of suspected infection (7,23,27). Combining serum IL-8 with CRP improved the sensitivity from 83 to 93% without losing much specificity (7).…”

Section: Discussionmentioning

confidence: 98%

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

et al. 2004

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Plasma IL-8 is a diagnostic parameter of early-onset bacterial infection (EOBI) in neonates but has a short half-life. The detergent-lysed whole-blood (DLWB) IL-8 consists of both extracellular and cell-bound IL-8. The objective of this study was to investigate kinetics of plasma and DLWB IL-8 in healthy newborns and those with suspected EOBI and to test the hypothesis that determination of DLWB IL-8 results in higher sensitivity for EOBI detection. Sixty-one neonates with clinical and serologic signs of EOBI composed the study group; 188 neonates with risk factors but without EOBI served as control subjects. IL-8 concentrations were determined in plasma and DLWB. In the control group, DLWB IL-8 concentrations were 280-fold higher (9599 pg/mL; SD 4433) up to 24 h post partum than corresponding plasma levels (34.2 pg/mL; SD 18.1). The sensitivity of DLWB versus plasma IL-8 for EOBI was 0.97 versus 0.71 after 6 h and 0.70 versus 0.32 after 24 h. Corresponding values for specificity were 0.95 versus 0.90 after 6 h and 0.92 versus 0.99 after 24 h. After 24 h, the negative predictive value for DLWB versus plasma IL-8 was 0.80 versus 0.66. DLWB IL-8 showed a higher sensitivity for EOBI within 6 h after first clinical suspicion than plasma IL-8. It also remained elevated longer. Our results suggest that DLWB IL-8 results in a higher sensitivity for EOBI. Abbreviations CRP, C-reactive protein DLWB, detergent-lysed whole blood EOBI, early-onset bacterial infection I/T ratio, immature to total neutrophil ratio NPV, negative predictive value PPV, positive predictive value ROC, receiver operator characteristics Neonates are susceptible to infections (1). The differential diagnosis of early-onset bacterial infection (EOBI) therefore must always be present for the neonatologist, regardless of how minor, unexpected, or discrete the clinical symptoms. EOBI is usually defined as occurring up to 72 h after birth (2) and is associated with a high morbidity and mortality risk (1). The nonspecific clinical signs as well as the currently established biochemical and hematologic parameters have their diagnostic limitations (3,4) [reviewed in (5,6)].Plasma IL-8 is an appreciated, highly predictive, and easily accessible chemokine to detect EOBI (7). IL-8 secretion is not limited to infections (8 -10), yet it occurs within 1-3 h of endotoxin challenge (11). As with most cytokines, its plasma half-life is short (Ͻ4 h) (12,13). Circulating IL-8, which can be detected in plasma or serum via immunoassay, is immediately bound to two distinct high-affinity IL-8 receptors that are abundantly present on neutrophils before internalization and degradation (14,15). Therefore, plasma IL-8 reflects only a small portion of the total IL-8 blood pool, because the majority is cell associated (16 -18).Cell association is enhanced by chemokine binding, non-IL-8 -specific receptors. These have been identified on various cell types (19), including the Duffy antigen-related chemokine receptors (16), presented on erythrocytes. Duffy antigenrelated chemokine-li...

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Section: Discussionmentioning

confidence: 98%

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

et al. 2004

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“…Bacterial infection is still a major cause of perinatal morbidity and mortality, and the recognition of infection is difficult since the clinical and biochemical manifestations are subtle in the neonatal period [11]. New tools for diagnosing potentially life-threatening infections in these vulnerable patients are therefore needed [11].…”

Section: Introductionmentioning

confidence: 99%

“…New tools for diagnosing potentially life-threatening infections in these vulnerable patients are therefore needed [11].…”

Section: Introductionmentioning

confidence: 99%

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Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits

Rygg

1996

Clinical and Experimental Immunology

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SUMMARYSerum amyloid A (SAA) is an acute-phase plasma protein which increases 100-to 1000-fold in response to inflammatory stimuli. In this study pregnant rabbits were subjected to laparotomy and their fetuses were injected with lipopolysaccharide (LPS) or various cytokines. Newborn rabbits were likewise stimulated. Hepatic SAA mRNA was studied using Northern blot analyses and scanning densitometry. In vitro derived RNA was used as standard for quantitative mRNA analyses. Cytokine concentrations in amniotic fluid and serum were analysed by biological assays. Fetal rabbits responded to cytokine stimulation by increased hepatic SAA mRNA expression, both during late gestation and in the early neonatal period. However, differences in dose-responses, kinetics and mRNA concentrations were seen dependent on gestational age. IL-1 and tumour necrosis factor (TNF) induced hepatic accumulation of both SAA1, SAA2 and SAA3, while only SAA1 and SAA2 mRNA accumulation was seen after IL-6 stimulation. High levels of IL-1 and TNF found in amniotic fluid from LPS-stimulated fetal rabbits corresponded with high levels in fetal, but not in maternal, serum. High levels of IL-1 and TNF, but no IL-6, were seen in newborn control sera and in adult serum 1 day after a normal delivery. The study details the complexity of the cytokine-induced in vivo response of SAA mRNA in fetal and neonatal rabbits.

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“…Biomarkers are identified through a four-step process of discovery by appropriate multiplex biochemical analysis followed by replication ideally in independent cohorts, validation of diagnostic sensitivity and specificity, and translation into a clinical diagnostic test (9). Numerous candidate biomarkers have been identified in neonatal sepsis: elevated plasma or serum levels of inter-leukin 6 (IL-6) 1 (11,13), tumor necrosis factor ␣ (TNF␣) (11,13), neutrophil elastase (NE) (14), C-reactive protein (CRP) (12,15), soluble CD14 (16,17), granulocyte colony-stimulating factor (G-CSF) (18), soluble intercellular adhesion molecule-1 (ICAM-1) (12), and soluble L-selectin (19) have shown association with infection in neonates. The value of physiological measurements in this context has also been examined recently (20).…”

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confidence: 99%

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Kennedy

Halliday

Velkinburgh

et al. 2008

Molecular & Cellular Proteomics

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Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P-and E-selectins, interleukin 2 soluble receptor ␣, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

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Predictive Value of Soluble Immunological Mediators in Neonatal Infection

Cited by 48 publications

References 0 publications

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

Cytokine-induced differential expression of serum amyloid A genes in fetal and neonatal rabbits

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

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