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Human neutrophil lipocalin: normal levels and use as a marker for invasive infection in the newborn
Department of Paediatrics, Örebro University Hospital, Örebro.
Department of Infectious Diseases, Örebro University Hospital, Örebro.
Women's and Children's Health, Section for Paediatrics, University Hospital, Uppsala, Sweden.
Medical Sciences and Clinical Chemistry, University Hospital, Uppsala, Sweden.
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2004 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 93, no 4, 534-539 p.Article in journal (Refereed) Published
Abstract [en]

Aim: To evaluate human neutrophil lipocalin (HNL) as a marker of neonatal invasive infection and determine the normal serum levels of HNL in newborns.

Methods: HNL is released from neutrophil granulocytes and is regarded as a specific marker of neutrophil activity. In 81 newborns 28 d of age with signs of infection on a total of 87 occasions, HNL and C-reactive protein (CRP) were measured at inclusion and on the three following days. As controls, term healthy newborns were recruited at birth (cord blood, n= 45) and at ages 3-5 d (n= 46). Serum HNL was measured by a radioimmunoassay.

Results: 25/87 episodes were classified as infection and 62 as non-proven infection. HNLmax was significantly higher in the infected group (mean 587.6 μg/1) than in the non-proven infected group (mean 217.7 μg/1, p > 0.001). HNL peaked at inclusion, 1 d earlier than CRP. In the healthy controls, HNL was the same at 3-5 d of age as at birth (mean 82.4-81.7 μg/1) and similar to normal adult levels.

Conclusions: The release of HNL is not increased in healthy newborns at birth, but neonatal neutrophils rapidly release HNL upon microbial stimulation in vivo. HNL might be useful as an early marker of neonatal infection.

Place, publisher, year, edition, pages
2004. Vol. 93, no 4, 534-539 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-85066DOI: 10.1080/08035250410024754OAI: diva2:564039
Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2012-11-01
In thesis
1. Coagulase-negative staphylococci septicaemia in newborns: aspects on host-bacterial interactions with special regard to neutrophil and endothelial response
Open this publication in new window or tab >>Coagulase-negative staphylococci septicaemia in newborns: aspects on host-bacterial interactions with special regard to neutrophil and endothelial response
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Newborn infants, especially those born preterm, are immunologically immature and prone to invasive infections. As a result of the increasing survival of very preterm (VPT < 31 weeks gestational age) newborns, nosocomial septicaemia has become a major concern the neonatal intensive care, and coagulase-negative staphylococci (CoNS) are nowadays the most frequently isolated pathogens in neonatal blood cultures. Further insight into host-bacterial interactions is required for the development of preventive strategies against CoNS septicaemia in VPT newborns.

Aim of the study: To investigate host-bacterial interactions in neonatal CoNS septicaemia with special regard to the neutrophil and endothelial response and to bacterial virulence factors.

Methods and results: Neonatal blood isolates of CoNS collected at Örebro University Hospital, Örebro, Sweden during the years 1983-1997 were characterised clinically and according to species and to phenotypic and genotypic patterns. Biochemial fingerprinting was found useful as a screening tool for selection of phenotypically related strains, but for further discrimination within a phenotypic cluster, genetic fingerprinting by pulsed field gel electrophoresis (PFGE) was required.

The isolates of S. epidermidis collected during the later part of the study period (1990-1997, n = 50) were further investigated. A hypervirulent clone of bacteria was identified, representing 7 of the 12 sepsis isolates in that cohort. These 12 isolates of S. epidermidis induced significantly higher endothelial release of neutrophil chemoattractants from human umbilical vein endothelial cell (HUVEC) cultures than did the isolates regarded as skin contaminants (n = 38). There were no differences between the sepsis and contaminant groups in the prevalence of genes for biofilm production, methicillin resistance or fibrinogen-binding protein.

The neutrophil oxidative burst occuring after stimulation by different bacterial strains was investigated by a flow cytometric method applied to a whole blood model. The oxidative activity in unstimulated neutrophils was similar in term (n = 10) and preterm (n = 10) newborns. However, the term newborns showed a significantly higher capacity to up-regulate the oxidative burst after bacterial stimulation. Significant differences in oxidative responses to different bacterial strains were observed, but these differences could not be related exclusively to species or invasive capacity.

A neutrophil granule protein, human neutrophil lipocalin (HNL), was evaluated as an early marker of neonatal septicaemia in newborns with clinical signs of infection. The serum level of HNL was significantly higher in the infected group of neonates (n = 25) than in the group with non-proven infection (n = 62). In healthy term controls the HNL level was similar at age 3 days to that at birth and close to the level reported in healthy adults.

Conclusions: The increased up-regulation of endothelial inflammatory mediators induced by sepsis isolates of S. epidermidis represents an important step in the pathogenesis of neonatal CoNS septicaemia. HNL might be useful as a marker of neutrophil activity also in VPT newborns. The laboratory assays used in the present study can be further developed for future investigations of the pathogenesis and host-bacterial interactions in neonatal CoNS septicaemia.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2004. 70 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 861
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-22100 (URN)1194 (Local ID)91-7373-836-0 (ISBN)1194 (Archive number)1194 (OAI)
Public defence
2004-10-15, B-husets aula, Universitetssjukhuset, Örebro, 09:00 (Swedish)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-11-01Bibliographically approved

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