Association of Circulating C-C Motif Chemokine Ligand 4 to Disease Severity and Clinical Outcomes in Sepsis: A Prospective Observational Study

Background: Sepsis is a life-threatening syndrome characterized by a dysregulated host response and organ dysfunction and remains a major cause of mortality in intensive care units (ICUs). Early risk stratification is essential for clinical management. C-C motif chemokine ligand 4 (CCL4), a pro-inflammatory chemokine involved in immune cell recruitment, may reflect the severity of systemic inflammation; however, its prognostic value in adult patients with sepsis has not been fully elucidated. Methods: In this prospective, single-center observational study, 75 adult patients with sepsis admitted to the ICU were enrolled. Plasma CCL4 levels were measured at admission using an enzyme-linked immunosorbent assay (ELISA). Logistic regression, receiver operating characteristic (ROC) curve analysis, DeLong testing, and reclassification analyses using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were performed. Results: CCL4 levels were significantly higher in non-survivors than survivors (1784 ± 752 vs. 1397 ± 528 pg/mL, p = 0.011). In multivariable analysis, the CCL4 (odds ratio [OR] 1.001, p = 0.023) and Pitt bacteremia score (OR 1.523, p = 0.003) were independently associated with ICU mortality. CCL4 alone showed modest discriminative performance (AUC 0.645, 95% confidence interval [CI] 0.508–0.782). However, the addition of CCL4 to clinical severity scores significantly improved discrimination, with the highest observed in the combined model (AUC 0.885). Reclassification analyses further supported the incremental prognostic value of CCL4. Conclusions: CCL4 is independently associated with ICU mortality in sepsis, and its integration with clinical severity scores may improve prognostic accuracy for risk stratification.