INTERLEUKIN-1 RECEPTOR ANTAGONIST AND INTERLEUKIN-6 FOR EARLY DIAGNOSIS OF NEONATAL SEPSIS 2 DAYS BEFORE CLINICAL MANIFESTATION

Background Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic the rapy 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 pow er of the early inflammatory mediators interleukin-1 receptor antagoni st (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhes ion molecule-1 (cICAM-1) before clinical diagnosis of sepsis. Methods In a prospective multicentre study, we monitored 182 very-low-birthwei ght infants in six intensive-care units for occurrence of sepsis. Duri ng routine or clinically indicated blood sampling, an additional sampl e was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reacti ve protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Wh enever sepsis occurred, a study period of 10 days was defined: day 0 w as the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 d ays before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study pe riod with group-specific baseline values from before day -4. Findings 101 infants were included in the analysis: 21 with proven sepsis, 20 w ith no infection, and 60 unclassified. We excluded 57 because of incom plete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 incr eased 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 concen trations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; c orresponding values on day -1 were 64%, 57%, and 18%. The specificitie s of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICA M-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 bef ore clinical diagnosis. Ad-hoc measurement of these cytokines could al low earlier initiation of antibiotic therapy with corresponding improv ement in outcome in very-low-birthweight infants with sepsis.