Prospective observational study of inflammatory mediators in adult ED patients with suspected infectionBlood protein patterns in sick ER patients hint at who might survive

medRxiv Published April 21, 2026 Study authors: Cistero, B.; Monforte, V.; Camprubi-Rimblas, M.; Areny-Balaguero, A.; Campana-Duel, E.; Fernandez, A… DOI ↗ Editorial oversight: Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

AI-generated summary of the cited source, checked by automated accuracy review. How we work

Key Takeaway

Consider that inflammatory mediator dynamics in this single-centre observational study show associations but not causation with sepsis and organ dysfunction.

This is a single-centre, prospective observational study in an Emergency Department, examining 173 adult patients with suspected infection and a National Early Warning Score 2 (NEWS 2) of 3 or higher. The study measured longitudinal inflammatory mediators (IL10, IL1RN, IL6, IL8, CCL2, TNFRSF1A, PCT) over 24 hours and assessed associations with in-hospital mortality, sepsis diagnosis, and organ dysfunction severity.

Key findings include time-dependent decreases in IL10 (beta -0.016, 95%CI -0.028 to -0.004), IL1RN (beta -0.014, 95%CI -0.024 to -0.004), and IL6 (beta -0.012, 95%CI -0.024 to 0.00). Sepsis was associated with higher levels of IL1RN (beta 0.378, 95%CI 0.153-0.603) and TNFRSF1A (beta 0.40, 95%CI 0.21-0.58). Organ dysfunction (SOFA score) correlated with elevated levels of IL10, IL1RN, CCL2, TNFRSF1A, and PCT, with PCT showing the strongest association (beta 2.63, 95%CI 1.32-3.93).

Survival models indicated IL8 (HR 0.655, 95% CrI 0.582-0.728) and TNFRSF1A (HR 0.505, 95% CrI 0.419-0.682) were protective, while PCT was neutral (HR 1.004, 95% CrI 1.001-1.008). Sepsis incidence was 79% (137/173 patients). The authors note that TNFRSF1A, IL8, and PCT dynamics could inform prognosis tools.

Limitations include the single-centre design, observational nature precluding causal inference, and lack of reported safety data. The study used linear mixed models and joint survival models, with results not generalizable beyond this setting. Practice relevance is restrained to hypothesis generation for prognostic tools.

When someone arrives at the ER with a serious infection, doctors need to know who might get worse. This study tracked proteins in the blood that signal inflammation over the first 24 hours in 173 adults who came to the ER with suspected infection and a high warning score.

Researchers found that levels of several proteins, like IL10 and IL6, tended to drop over time. Other proteins, like IL1RN and TNFRSF1A, were higher in patients who developed sepsis. Some proteins, including IL8 and TNFRSF1A, were linked to a better chance of survival, while PCT showed a very slight increase linked to survival. The study also found that certain proteins correlated with the severity of organ dysfunction.

This was a single-center, observational study, so it shows associations, not cause and effect. The findings are based on statistical models and may not apply to other hospitals. Still, the patterns suggest that tracking these proteins could help develop tools to predict outcomes for patients with serious infections.

What this means for you:

Blood protein changes in ER patients with infection may help predict who survives.

Study Details

Sample sizen = 173

EvidenceLevel 5

PublishedApr 2026

View Original Abstract ↓

Sepsis is a complex condition with a time-dependent evolution. Longitudinal biomarker dynamics could help us to better characterise sepsis. We hypothesised that the kinetics of biomarkers are associated with sepsis and with the intensity of organ dysfunction, and may have predictive capacity for patient survival. This single-centre, prospective, observational study included adult patients presenting to the Emergency Department (ED) with suspected infection. Patients were included in the study if they had a National Early Warning Score 2 (NEWS 2) of 3 or higher. Blood samples were obtained at baseline, 4hs and 24 hs. Linear mixed models were constructed to analyse the association between biomarker concentrations over time, sepsis diagnosis and organ dysfunction severity. Joint models were used to evaluate the predictive ability of individual biomarker kinetics during the first 24 hours for in-hospital mortality Of 214 screened patients, 173 patients were analysed, and 137 (79%) developed sepsis. Linear mixed models revealed time-dependent decreases in IL10 ({beta} -0.016, 95%CI -0.028 to -0.004), IL1RN ({beta} -0.014, 95%CI -0.024 to -0.004), and IL6 ({beta} -0.012, 95%CI -0.024 to 0.00). Sepsis was associated with higher IL1RN ({beta} 0.378, 95%CI 0.153-0.603), and TNFRSF1A ({beta} 0.40, 95%CI 0.21-0.58); only models evaluating IL6 showed significant interaction between sepsis and time ({beta} -0.14, 95%CI -0.028 to 0.00). SOFA correlated with elevated IL10 ({beta} 0.048, 95%CI 0.021-0.075), IL1RN ({beta} 0.044, 95%CI 0.017-0.071), CCL2 ({beta} 0.046, 95%CI 0.021-0.071), TNFRSF1A ({beta} 0.050, 95%CI 0.030-0.070), and PCT ({beta} 2.63, 95%CI 1.32-3.93); the interaction between SOFA score and time was significant only for IL6 ({beta} -0.003, 95%CI -0.005 to -0.001). Joint survival models (adjusted for age and highest SOFA) identified IL8 (HR 0.655, 95% CrI 0.582-0.728), TNFRSF1A (HR 0.505, 95% CrI 0.419-0.682), and PCT (HR 1.004, 95% CrI 1.001-1.008) as predictors. ConclusionSepsis diagnosis and severity of organ dysfunction may be associated with higher levels and kinetic values of inflammatory biomarkers such as IL1RN and TNFRSF1A. IL6 levels showed a significant association for the interaction of time with both sepsis diagnosis and SOFA score. TNFRSF1A, IL8 and PCT dynamics were found to be associated with survival and could be useful in developing prognosis tools.

Prospective observational study of inflammatory mediators in adult ED patients with suspected infectionBlood protein patterns in sick ER patients hint at who might survive

Study Details

Intraosseous route for out-of-hospital cardiac arrest linked to lower outcomes than intravenous access

Using a bone needle instead of a vein line lowers survival chances for cardiac arrest patients

Clinical research that matters. Delivered to your inbox.

Prospective observational study of inflammatory mediators in adult ED patients with suspected infectionBlood protein patterns in sick ER patients hint at who might survive

More on Sepsis

Study Details

Intraosseous route for out-of-hospital cardiac arrest linked to lower outcomes than intravenous access

Using a bone needle instead of a vein line lowers survival chances for cardiac arrest patients

Clinical research that matters. Delivered to your inbox.

Related in Emergency Medicine

From Other Specialties