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

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

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

Prompt diagnosis is critical, yet challenging, due to the non-specific symptoms of sepsis and the limitations of traditional diagnostic biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT), which have delayed responses and suboptimal sensitivity. Given the rapid progression of sepsis, there is an urgent need for biomarkers that offer faster, 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 evaluated through AUROC analysis (ranging from 1.0, a perfect test with 100% specificity and sensitivity, to 0.5, a completely ineffective test).

IL-6 consistently outperformed traditional biomarkers in distinguishing bacterial from non-bacterial 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, distinguishing between mild infection, sepsis, and septic shock, a critical capability for guiding timely and appropriate treatment.

In terms of sensitivity and specificity, IL-6 exceeded 80% in both paediatric and maternal patients, detecting bacterial infections with 91% sensitivity 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 partly attributable to the complexities of diagnosing neonatal sepsis, where there is no clear consensus definition. The broader spectrum of presentations in neonatal sepsis may also contribute to these differences. 

Discussing the advantages of IL-6 over traditional biomarkers, Dr. Seán Whelan, lead author, explained, "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."

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

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."

Dr. Seán Whelan, lead author