Early immune alarm molecule predicts death after heart attacks

When a heart attack strikes, the body launches an immune response within minutes, and new research suggests that the earliest wave of that response may hold the key to predicting which patients will survive the following year. A study drawing on the Swiss SPUM-ACS cohort has found that elevated levels of interleukin-8, a potent chemokine that mobilizes neutrophils to sites of tissue injury, are independently associated with one-year mortality in patients experiencing acute myocardial infarction. The findings, published in Clinical Research in Cardiology, position IL-8 as a potential early warning signal that rises well before troponin, the standard marker of heart muscle damage, becomes detectable.

The research team, led by investigators at the University Hospital Zurich, examined 112 patients who died or suffered a recurrent myocardial infarction within one year of their initial event, matching each case one-to-one with a control patient of the same age, sex, infarct subtype, symptom-onset timing, and recruiting site. All blood samples were drawn within 24 hours of symptom onset, capturing the inflammatory landscape at a moment when standard clinical markers had often not yet begun their climb. Compared with controls, the patients who later experienced adverse outcomes had significantly higher plasma concentrations of IL-8, cell-free DNA, and myeloperoxidase, along with a higher neutrophil-to-lymphocyte ratio.

These three soluble markers tell a coherent biological story. Interleukin-8, also known as CXCL8, is released by endothelial cells, monocytes, and macrophages at the first sign of injury and creates a chemical gradient that draws neutrophils to the damaged myocardium. Once there, neutrophils expel neutrophil extracellular traps, web-like structures composed of cell-free DNA studded with enzymes such as myeloperoxidase. Although these traps serve a protective purpose against pathogens, in the setting of atherosclerosis they can activate platelets and coagulation factors, potentially worsening the very thrombotic process that caused the infarction. The simultaneous elevation of IL-8, cfDNA, and MPO in patients who fared poorly points to a hyperactive IL-8 and NET axis operating in the hours immediately after coronary occlusion.

Perhaps the most striking finding concerns timing. When patients were stratified by how quickly they reached the hospital after symptoms began, IL-8 levels were already significantly elevated in those presenting within three hours, whereas high-sensitivity troponin T only became clearly discriminative in late presenters beyond six hours. Within the hyper-acute window, IL-8 outperformed troponin, NT-proBNP, C-reactive protein, and kidney function markers in distinguishing future events from stable outcomes. After adjusting for these confounders, the association between IL-8 and the combined endpoint of death or recurrent infarction was strongest among early presenters, with an odds ratio of 2.65 for patients arriving within six hours of symptom onset.

The temporal analysis extended to the prognosis itself. When the researchers focused on early adverse events occurring within thirty days, the association between IL-8 and risk strengthened markedly, reaching an adjusted odds ratio of 4.47. A formal statistical test confirmed a significant interaction between IL-8 levels and symptom-onset time, meaning that the predictive value of this chemokine is genuinely tied to how early in the disease course the measurement is taken. This finding carries practical implications, because the first hours after symptom onset have long been a diagnostic blind spot in which traditional biomarkers lag behind the rapidly evolving pathology.

Within the group of patients who experienced adverse outcomes, those who died had higher IL-8 and cfDNA levels than those who survived with a recurrent infarction, suggesting that fatal outcomes are characterized by an even more intense neutrophil-driven inflammatory response. The neutrophil-to-lymphocyte ratio, a simple calculation available from any standard blood count, was likewise higher in the death subgroup, echoing results from large trials such as CANTOS, where each quartile increase in this ratio corresponded to a roughly twenty percent rise in major adverse cardiovascular events.

Unsupervised clustering of the inflammatory data added another layer of insight. When patients were grouped according to their combined profiles of IL-8, cfDNA, neutrophil-to-lymphocyte ratio, and high-sensitivity C-reactive protein, one cluster was significantly enriched in patients presenting with acute heart failure, defined clinically as a Killip Class of two or higher, and in those who ultimately died. This overlap between systemic inflammation and acute heart failure suggests that high IL-8 levels may partly reflect the mechanistic basis of pump dysfunction rather than merely accompanying it, although the observational design of the study cannot resolve whether inflammation causes heart failure or simply mirrors it.

The researchers also tested whether adding IL-8 to the widely used GRACE 2.0 risk score would improve its predictive accuracy. After rigorous cross-validation, neither IL-8 alone nor the combined panel of inflammatory markers produced a statistically significant improvement over the existing score for the overall cohort, likely because the score already captures much of the relevant risk and because late presenters diluted the hyper-acute signal. The authors therefore frame IL-8 not as a universal upgrade to existing risk tools but as a precision-medicine candidate for the specific subgroup of patients who present within hours of symptom onset.

Several caveats temper the enthusiasm. The study was observational and matched by design, so it cannot establish causality, and the lack of an IL-8 gene in mice complicates experimental efforts to probe the chemokine’s role directly. Genetic association studies hint that polymorphisms in the IL-8 promoter influence both circulating levels and acute coronary syndrome risk, but larger studies will be needed to determine whether IL-8 drives worse outcomes or simply reports on them. The authors also note that no clinical cutoff value for IL-8 can be proposed from a case-control design, and external validation in an independent cohort remains essential.

Even so, the prospect of a point-of-care IL-8 test, paired with the humble neutrophil-to-lymphocyte ratio, offers a tantalizing vision for emergency cardiology: a rapid, early, and biologically grounded assessment of risk during the very first hours of a heart attack, when every clinical decision carries the greatest weight. Therapies targeting IL-8 signaling are already being explored in oncology, and this study adds urgency to investigating whether similar approaches might one day quiet the inflammatory storm that follows myocardial infarction.

Subject of Research: Interleukin-8 and neutrophil-related biomarkers as prognostic markers for one-year mortality after acute myocardial infarction

Article Title: Interleukin-8 and other neutrophil-related biomarkers are associated with 1-year mortality in patients with acute myocardial infarction

Article References: Wang, Y.-J., Matter, M. A., Rossi, V. A., Heg, D., Costantino, S., Paneni, F., Gallino, C., Stähli, B. E., Räber, L., Windecker, S., Mach, F., Gencer, B., Klingenberg, R., Rodondi, N., Nanchen, D., Levesque, M. P., Demler, O. V., Ruschitzka, F., & Matter, C. M. (2026). Interleukin-8 and other neutrophil-related biomarkers are associated with 1-year mortality in patients with acute myocardial infarction. Clinical Research in Cardiology. https://doi.org/10.1007/s00392-026-03026-x

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03026-x

Keywords: interleukin-8, acute myocardial infarction, neutrophils, neutrophil extracellular traps, cell-free DNA, myeloperoxidase, neutrophil-to-lymphocyte ratio, biomarkers, mortality, inflammation, GRACE 2.0, cardiology