IL-6 Outperforms Traditional Tests for Early Sepsis Detection

Sepsis, a severe and life-threatening condition caused by the immune system’s exaggerated response to infection, remains a major cause of death globally, responsible for approximately 11 million fatalities each year. Children under five and pregnant women are particularly vulnerable due to immune system changes and heightened susceptibility to infections. Diagnosing sepsis in pregnant women is especially difficult, as the physiological changes during pregnancy can obscure early signs of the condition. Timely diagnosis is critical but challenging, as the symptoms of sepsis are often nonspecific, and conventional biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) have delayed responses and limited sensitivity. Given the rapid progression of sepsis, there is a pressing need for biomarkers that offer faster, more precise diagnostic capabilities to allow for prompt intervention. Now, a groundbreaking study presented at ESCMID Global 2025 has highlighted the potential of interleukin-6 (IL-6) as an effective diagnostic biomarker for early sepsis detection in high-risk patient groups, such as neonates, children, and pregnant women. This study is the first to assess IL-6’s diagnostic performance in a real-world cohort involving all three populations.

In this retrospective cohort study, researchers from CHI at Temple Street (Dublin, Ireland) analyzed serial blood samples from 252 patients—111 pediatric, 72 maternity, and 69 neonatal cases—who were suspected of having sepsis. The patients were classified based on infection type (bacterial, viral, or no infection) and physiological response (normal, systemic inflammatory response syndrome, sepsis, and septic shock). The diagnostic accuracy of IL-6 was assessed using AUROC analysis (ranging from 1.0, representing a perfect test, to 0.5, indicating a completely ineffective test). IL-6 consistently outperformed traditional biomarkers in distinguishing bacterial infections from non-bacterial ones, with AUROC values of 0.91 in children, 0.94 in maternal patients, and 0.86 in neonates.

IL-6 was also able to effectively differentiate the severity of sepsis, distinguishing between mild infection, sepsis, and septic shock, which is crucial for ensuring timely and appropriate treatment. Regarding sensitivity and specificity, IL-6 exceeded 80% in both pediatric and maternal patient groups, detecting bacterial infections with 91% sensitivity in children and 94% sensitivity in pregnant women. In neonates, while IL-6 maintained high specificity (97.1%), its sensitivity (67.6%) was lower. The reduced sensitivity and AUROC values in neonates may be partly due to the challenges in diagnosing neonatal sepsis, where there is no universally accepted definition. The wider range of presentations seen in neonatal sepsis may also account for these differences.

“IL-6 secretion rises within 1-2 hours, peaks at 6 hours and decreases by 24 hours, whereas CRP and PCT peak much later at 48 and 24 hours, respectively. This faster, steeper response makes IL-6 a promising biomarker for earlier sepsis detection,” said Dr. Seán Whelan, lead author of the study. “Our findings reinforce the potential of IL-6 as a promising biomarker in sepsis diagnosis. With wider adoption and in combination with clinical assessment, IL-6 could significantly improve clinical decision-making and support timely, targeted treatment for high-risk patients.”

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