IL-6 emerges as an early sepsis indicator in high-risk groups

IL-6 emerges as an early sepsis indicator in high-risk groups

A landmark study presented today at ESCMID Global 2025 has revealed the potential of interleukin-6 (IL-6) as a powerful diagnostic biomarker for the early detection of sepsis in high-risk patient populations, including newborns, children and pregnant women. This study is the first to evaluate the diagnostic performance of IL-6 in a real-world cohort in all three populations.

Sepsis, a life-threatening condition resulting from the immune system's overreaction to infection, remains a leading cause of mortality worldwide, accounting for an estimated 11 million deaths each year. Young children, especially those under five, and pregnant women are highly vulnerable due to immunological changes and increased susceptibility. Diagnosing sepsis during pregnancy is particularly difficult because physiological changes can obscure its early signs.

Immediate diagnosis is difficult due to the nonspecific symptoms of sepsis and the limitations of traditional diagnostic biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), which exhibit delayed responses and suboptimal sensitivity. Given the rapid progression of sepsis, there is an urgent need for biomarkers that provide faster and more accurate diagnosis to enable timely intervention.

The retrospective cohort study analyzed serial blood samples from 252 patients (111 pediatric, 72 maternity and 69 neonatal cases) with suspected sepsis. Patients were classified by infection type (bacterial, viral, or no infection) and physiological response (normal, systemic inflammatory response syndrome, sepsis, and septic shock). Diagnostic accuracy was assessed by AUROC analysis (from 1.0, a perfect test with 100% specificity and sensitivity, to 0.5, a completely ineffective test).

IL-6 outperformed traditional biomarkers in distinguishing bacterial from nonbacterial infections, with AUROC values ​​of 0.91 in children, 0.94 in maternal patients, and 0.86 in neonates. IL-6 also effectively stratified sepsis severity and differentiated between mild infection, sepsis, and septic shock, a critical ability for timely and appropriate treatment.

In terms of sensitivity and specificity, IL-6 exceeded over 80% in both pediatric and maternal patients, which has detected bacterial infections with a sensitivity of 91% in children and 94% in pregnant women. In neonates, while IL-6 maintained high specificity (97.1%), its sensitivity (67.6%) was lower. These lower sensitivity and AUROC values ​​may be due in part to the complexity of diagnosing neonatal sepsis, where there is no clear consensus definition. The broader range of presentations in neonatal sepsis may also contribute to these differences.

Discussing the advantages of IL-6 over traditional biomarkers, Dr. Seán Whelan, senior author, explained,"IL-6 secretion increases within 1-2 hours, peaking at 6 hours and decreasing by 24 hours, while 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.“

Dr. Whelan also highlighted its growing clinical application. “IL-6 is already in routine use for these populations at our institutions, the Rotunda Hospital and Children’s Health Ireland on Temple Street. Challenges to wider adoption have been reduced by the development of commercially available tests on commonly used platforms that can provide real-time results. The Covid-19 pandemic accelerated this process as IL-6 testing became more widely used in assessing patients' inflammation. “

Our results reinforce the potential of IL-6 as a promising biomarker in sepsis diagnosis. With wider adoption and in combination with clinical evaluation, IL-6 could significantly improve clinical decision-making and support timely and targeted treatment of high-risk patients. “

Dr. Seán Whelan, lead author

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