Early diagnostic markers for neonatal sepsis Comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules

Døllner, Henrik; Vatten, Lars J.; Austgulen, Rigmor

doi:10.1016/s0895-4356(01)00400-0

Cited by 143 publications

(125 citation statements)

References 30 publications

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“…These patients would most likely benefit from a reduction of the inflammatory response. As the recent Lenercept trial shows (58), the 6 -72 h (postinjection) serum concentrations achieved with recombinant soluble TNF SR I (p55) during the treatment for human sepsis were substantially higher (by 2-3 logs) than the post-CLP concentration of endogenous TNF SR I observed here and in human sepsis (59,60). Hence, it is unlikely that the treatment failure was due to the inadequate supplementation of the endogenous pool of TNF SR I with the exogenous TNFR.…”

Section: Discussionmentioning

confidence: 44%

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

Osuchowski

Welch

Siddiqui

et al. 2006

The Journal of Immunology

468

379

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Mortality in sepsis remains unacceptably high and attempts to modulate the inflammatory response failed to improve survival. Previous reports postulated that the sepsis-triggered immunological cascade is multimodal: initial systemic inflammatory response syndrome (SIRS; excessive pro-, but no/low anti-inflammatory plasma mediators), intermediate homeostasis with a mixed anti-inflammatory response syndrome (MARS; both pro- and anti-inflammatory mediators) and final compensatory anti-inflammatory response syndrome (CARS; excessive anti-, but no/low proinflammatory mediators). To verify this, we examined the evolution of the inflammatory response during the early phase of murine sepsis by repetitive blood sampling of septic animals. Increased plasma concentrations of proinflammatory (IL-6, TNF, IL-1β, KC, MIP-2, MCP-1, and eotaxin) and anti-inflammatory (TNF soluble receptors, IL-10, IL-1 receptor antagonist) cytokines were observed in early deaths (days 1–5). These elevations occurred simultaneously for both the pro- and anti-inflammatory mediators. Plasma levels of IL-6 (26 ng/ml), TNF-α (12 ng/ml), KC (33 ng/ml), MIP-2 (14 ng/ml), IL-1 receptor antagonist (65 ng/ml), TNF soluble receptor I (3 ng/ml), and TNF soluble receptor II (14 ng/ml) accurately predicted mortality within 24 h. In contrast, these parameters were not elevated in either the late-deaths (day 6–28) or survivors. Surprisingly, either pro- or anti-inflammatory cytokines were also reliable in predicting mortality up to 48 h before outcome. These data demonstrate that the initial inflammatory response directly correlates to early but not late sepsis mortality. This multifaceted response questions the use of a simple proinflammatory cytokine measurement for classifying the inflammatory status during sepsis.

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Section: Discussionmentioning

confidence: 44%

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

Osuchowski

Welch

Siddiqui

et al. 2006

The Journal of Immunology

468

379

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“…Separate studies showed that increased concentrations at birth decreased substantially in both term and preterm septic neonates during the first 24 h of life (28,71,72 ). An additional study found increased concentrations in septic preterm but not in full-term infants (68 ).…”

Section: Biomarker Detectionmentioning

confidence: 91%

Toward Resolving the Challenges of Sepsis Diagnosis

Scott²,

2004

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Sepsis in the UnitedStates has an estimated annual healthcare cost of $16.7 billion and leads to 120 000 deaths. Insufficient development in both medical diagnosis and treatment of sepsis has led to continued growth in reported cases of sepsis over the past two decades with little improvement in mortality statistics. Efforts over the last decade to improve diagnosis have unsuccessfully sought to identify a "magic bullet" proteic biomarker that provides high sensitivity and specificity for infectious inflammation. More recently, genetic methods have made tracking regulation of the genes responsible for these biomarkers possible, giving current research new direction in the search to understand how host immune response combats infection. Despite the breadth of research, inadequate treatment as a result of delayed diagnosis continues to affect approximately one fourth of septic patients. In this report we review past and present diagnostic methods for sepsis and their respective limitations, and discuss the requirements for more timely diagnosis as the next step in curtailing sepsis-related mortality. We also present a proposal toward revision of the current diagnostic paradigm to include real-time immune monitoring.

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“…Many possible markers of early infection have been investigated so far, yielding variable results, in search of a rapid, specific and sensitive test that would ensure early treatment and reduce unnecessary prophylactic treatment (3,4,5,6). Many humoral factors, recently even contents of their mRNA, have been measured, attempting to discover the immune reaction as early as possible.…”

Section: Discussionmentioning

confidence: 99%

Surface Activation Leukocyte Markers and Humoral Factors in Cord Blood of Newborns at Risk of Early Infection

Rozsíval

Parízková

Vokurková

et al. 2007

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary: Due to immaturity of both specific and non-specific immune mechanisms, neonates are at risk of serious infections. The risk group definition is vague, clinical signs are non-specific and common laboratory markers are not as useful as in later ages, especially due to delayed reactions. In an attempt to find early, sensitive and specific markers, we assessed a defined set of surface leukocyte markers and humoral factors in cord blood. Several differences were noted -children in the risk group had a higher proportion of CD19+/23+, CD16+/64+, CD45RO cells and higher levels of IL-6. We find it promising that already at birth there are notable signs of reaction to infection and that a follow-up of a set of infectious markers could be useful to identify the children in need of antibiotic treatment and for diminishing unnecessary treatment.

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Early diagnostic markers for neonatal sepsis Comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules

Cited by 143 publications

References 30 publications

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

Circulating Cytokine/Inhibitor Profiles Reshape the Understanding of the SIRS/CARS Continuum in Sepsis and Predict Mortality

Toward Resolving the Challenges of Sepsis Diagnosis

Surface Activation Leukocyte Markers and Humoral Factors in Cord Blood of Newborns at Risk of Early Infection

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