Sepsis remains a leading global cause of mortality, accounting for around 11 million deaths annually. In an attempt to improve detection of this life-threatening condition, a team of researchers in Dublin, Ireland, tested the biomarker performance of Interleukin-6 (IL-6). We connected with Sean Whelan, lead author of this study, to learn more about the findings.
What motivated you to focus on sepsis in neonates, children, and pregnant women specifically?
Diagnosing sepsis accurately and quickly in these groups is challenging. In neonates, confirmed sepsis is rare, so we often rely on clinical signs and biomarkers to guide treatment – but these tools aren’t always reliable. In children and pregnant women, many conditions can look like sepsis. For example, bleeding, eclampsia, or even labor in pregnancy can mimic sepsis symptoms, making diagnosis difficult. That’s why having reliable sepsis biomarkers for these populations is so important.
How does the study build on existing research on IL-6 as a biomarker?
Other studies have used IL-6 as a sepsis biomarker, which encouraged us to adopt it in our practice. What makes our study unique is that it looks at how IL-6 performs in everyday clinical settings, not just in controlled trials, and across three different patient groups.
How did IL-6 perform as a biomarker across the different patient groups?
Overall, IL-6 outperformed the other biomarkers we tested – CRP, PCT, and the neutrophil-lymphocyte ratio (NLR) – in all groups and for both diagnostic categories: physiological status and infection cause.
There were two exceptions, however, where IL-6 did not show a statistically significant advantage:
In pregnant women for assessing physiological status (normal, SIRS, sepsis, or septic shock), IL-6 and NLR performed similarly (area under the receiver operating characteristic curve [AUROC]: IL-6 = 0.78, NLR = 0.72).
In newborns, IL-6 and PCT also showed similar performance (AUROC: IL-6 = 0.86, PCT = 0.74).
How does this biomarker perform in differentiating between bacterial and viral infections?
We evaluated IL-6 in both pediatric and maternal patients. In children, IL-6 was highly effective at distinguishing bacterial from non-bacterial infections (including viral and no infection), with a sensitivity of 86 percent and specificity of 82 percent – better than CRP (77 percent sensitivity) and PCT (55 percent). The AUROC was 0.91, indicating excellent diagnostic accuracy.
In pregnant women, IL-6 also performed very well, with an AUROC of 0.94, sensitivity of 88 percent, and specificity of 91 percent. In contrast, CRP and PCT were much less reliable in this group – CRP had only 33 percent sensitivity, and PCT had 50 percent specificity.
It’s important to note that these results apply to patients already suspected of having sepsis. Although distinguishing bacterial from viral causes is also crucial in a broader population, that was not the focus of this study.
Can this test be utilized in other areas, such as low-resource or point-of-care settings?
We measured IL-6 using an electrochemiluminescence immunoassay, which runs on equipment already found in many medical labs. This makes adoption easier and allows for quick results. However, using this technology in low-resource settings is more difficult. Some studies have explored IL-6 test strips with optical readers as an alternative, but more research is needed before they can be used reliably in clinical practice.
Are there any pre-analytical or sample handling considerations that pathologists and lab staff should be aware of?
No, the testing was done by our clinical biochemistry team, including Professor Elsammak, a co-author and Consultant Chemical Pathologist. They were pleased with how well the assay performed. We've also extended testing hours to ensure results reach clinicians quickly, helping them care for these critically ill patients.
What’s next for this research?
We now use this biomarker regularly in our clinical practice, and it’s included in our hospital’s guidelines for managing suspected sepsis. Over time, more clinicians have started using it as they've seen its value, and test requests have increased.
From a research standpoint, we’d ideally like to see a prospective study to measure how IL-6 impacts patient outcomes and whether it’s cost-effective – but such a study would be a large effort, and as far as we know, none is currently planned.
Any expectations or hopes for the future of sepsis diagnosis?
My main hope is that pathologists can keep working closely with clinicians to improve early sepsis detection – especially in pregnant women and children, who are often underrepresented in research.
This study was presented at ESCMID Global 2025.
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