New Insights on IL-6 as an Early Biomarker for Sepsis in Vulnerable Populations

A recent study presented at the ESCMID Global 2025 conference has highlighted the potential of interleukin-6 (IL-6) as a significant biomarker for the early detection of sepsis in vulnerable groups, including neonates, children, and pregnant women. This marks the first thorough evaluation of IL-6's diagnostic efficacy in real-world settings across these three distinct populations.

Sepsis, characterized by the body's extreme response to infection, is a leading cause of mortality worldwide, claiming approximately 11 million lives each year. Young children, particularly those under the age of five, and pregnant women are at a heightened risk due to their unique immunological profiles and increased susceptibility to infections. Diagnosing sepsis in pregnant individuals poses additional challenges, as the physiological changes during pregnancy can mask the early signs of this serious condition.

Timely diagnosis is essential but complicated by the non-specific nature of sepsis symptoms and the limitations of established diagnostic markers like C-reactive protein (CRP) and procalcitonin (PCT), which often show delayed responses and lack optimal sensitivity. The rapid progression of sepsis underscores the urgent need for biomarkers that provide quicker and more accurate diagnostic capabilities to facilitate prompt treatment.

This retrospective cohort study analyzed serial blood samples from 252 patients suspected of having sepsis, categorized into 111 pediatric cases, 72 maternity cases, and 69 neonatal cases. The patients were further classified based on the type of infection (bacterial, viral, or non-infectious) and their physiological response (normal, systemic inflammatory response syndrome, sepsis, and septic shock). The diagnostic accuracy of IL-6 was assessed using the area under the receiver operating characteristic (AUROC) curve, which ranges from 1.0 (indicating a perfect test) to 0.5 (indicating no diagnostic value).

Findings revealed that IL-6 consistently surpassed traditional biomarkers in distinguishing between bacterial and non-bacterial infections. Specifically, the AUROC values were 0.91 for children, 0.94 for maternal cases, and 0.86 for neonates. Moreover, IL-6 was effective in stratifying the severity of sepsis, differentiating between mild infections, sepsis, and septic shock--crucial for guiding appropriate treatment decisions.

In terms of sensitivity and specificity, IL-6 demonstrated over 80% effectiveness in both pediatric and maternal patients, achieving 91% sensitivity for bacterial infections in children and 94% in pregnant women. While IL-6 showed high specificity (97.1%) in neonates, its sensitivity was lower at 67.6%. These variations in sensitivity and AUROC values in neonates may be attributed to the complexities involved in diagnosing neonatal sepsis, where definitions and presentations can vary significantly.

Discussing the advantages of IL-6 compared to traditional biomarkers, the study underscores that IL-6 levels rise within one to two hours following infection, peak at approximately six hours, and decline after 24 hours. In contrast, CRP and PCT levels peak later at 48 and 24 hours, respectively, making IL-6 a more promising candidate for early sepsis detection.

The clinical application of IL-6 is already gaining traction, as it is routinely used in institutions such as the Rotunda Hospital and Children's Health Ireland at Temple Street for these populations. The development of commercially available testing on widely used platforms has simplified its adoption, allowing real-time results. The COVID-19 pandemic further accelerated the use of IL-6 testing in assessing inflammation levels in patients.

These findings suggest that IL-6 holds considerable promise as a biomarker for sepsis diagnosis. With broader adoption and integration into clinical assessments, IL-6 could significantly enhance clinical decision-making and support timely, targeted interventions for high-risk patients.

For further information, please refer to the study by Whelan et al. presented at ESCMID Global 2025, Vienna, Austria.