Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation.

Abstract

BACKGROUND:

Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis.

METHODS:

In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4.

FINDINGS:

101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day -1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%.

INTERPRETATION:

IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.

• Authors: H Küster, M Weiss, A E Willeitner, S Detlefsen, I Jeremias, J Zbojan, R Geiger, G Lipowsky, G Simbruner
• Journal: Lancet (London, England) (Lancet) Vol. 352 Issue 9136 Pg. 1271-7 (Oct 17 1998) ISSN: 0140-6736 [Print] England
• PMID: 9788457 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• IL1RN protein, human
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-6
• Sialoglycoproteins
• Intercellular Adhesion Molecule-1
• C-Reactive Protein

Topics

• Austria
• Biomarkers (blood)
• C-Reactive Protein (metabolism)
• Diagnosis, Differential
• Female
• Germany
• Humans
• Infant, Newborn
• Infant, Very Low Birth Weight
• Intercellular Adhesion Molecule-1 (blood)
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-6 (blood)
• Male
• Prospective Studies
• Sensitivity and Specificity
• Sepsis (blood, diagnosis)
• Sialoglycoproteins (blood)
• Slovakia
• Time Factors