medwireNews: A real-world cohort study points to the potential of interleukin (IL)-6 as a biomarker to diagnose sepsis early in high-risk patient groups such as neonates, children, and pregnant women.
Speaking at ESCMID Global 2025 in Vienna, Austria, study author Seán Whelan (CHI at Temple Street and Rotunda Hospital, Dublin, Ireland) explained that “sepsis is a diagnostic challenge clinically” and “sepsis biomarkers therefore have been used as an adjunct to clinical assessment” to assist with diagnosis, prognostication, and de-escalation.
He added that IL-6 is a cytokine that has “gained some attention as a sepsis biomarker primarily because of its very attractive dose–response relationship.”
Specifically, while the levels of conventional biomarkers begin to rise 6–12 hours after an infectious insult and reach their peak 1–3 days after, IL-6 levels start to rise 1–2 hours after the insult and peak within 6 hours, said Whelan.
“This potentially more closely aligns with the physiological response and therefore may make the case for [IL-6] being a more sensitive, early diagnostic marker for sepsis,” he continued.
For the study, the team identified 245 patients (111 children, 72 pregnant women, and 62 neonates) from a specialist children’s hospital and a maternity hospital who underwent testing for IL-6 and other biomarkers to investigate suspected sepsis between March 2023 and March 2024.
Pediatric and maternal patients were categorized by physiological response (normal, systemic inflammatory response syndrome, sepsis, or septic shock) and infection etiology (no, viral, or bacterial infection), while neonates were classified according to a composite measure (no infection, clinical sepsis, or positive blood culture/septic shock).
Comparing IL-6 with currently used biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and neutrophil to lymphocyte ratio (NLR) showed that only IL-6 levels differed significantly across all categories for all populations.
Area under the receiver operating characteristic curve (AUROC) analysis revealed that IL-6 was significantly more accurate than other biomarkers at detecting the primary physiological outcome of sepsis or septic shock and the primary etiological outcome of bacterial infection in the pediatric population, at 85% versus 65%–72%, and 91% versus 69%–82%, respectively.
IL-6 also significantly outperformed the currently used markers with respect to the physiological and etiological endpoints in pregnant women, at AUROCs of 78% versus 51%–72%, and 94% versus 55%–69%, respectively. The only exception was the comparison with NLR to detect sepsis or septic shock, where there was no significant difference.
The AUROC for IL-6 to identify neonatal sepsis, as defined by the composite measure, was significantly higher than that for CRP and NLR, at 86% versus 65% and 68%, respectively, but not PCT, at 74%.
Whelan noted that generally “IL-6 had higher levels of sensitivity and specificity compared to the other biomarkers” in both the pediatric and maternal patient groups, with one exception being its specificity for sepsis or septic shock in the pregnant women, which, at 55.1%, was lower than that for the other biomarkers.
The sensitivity of IL-6 to diagnose neonatal sepsis was lower than for the other populations, but this was also the case for the other biomarkers and could be due to the complexities of diagnosing neonatal sepsis in the absence of a clear consensus definition, said the presenter.
Looking to the future, he highlighted the need to develop an individualized approach for biomarker assessment and added that there may be a case for a prospective study evaluating the impact on outcomes and antimicrobial use.
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