Targeting the trigger and the effector: The dual role of extracorporeal blood purification therapy in septic immune dysregulation.

Traditional Extracorporeal Blood Purification (EBP) rationales have focused on a concentration-dependent hypothesis of cytokine removal. However, emerging evidence suggests that a strictly plasma-centric interpretation is insufficient due to multicompartmental solute kinetics. This review proposes a comprehensive mechanistic framework for EBP, integrating mediator-directed and cell-directed immunomodulation. While mediator-directed therapies (e.g., AN69ST, PMMA membranes, and selective sorbents) aim to reduce the circulating burden of PAMPs and DAMPs, cell-directed interventions (e.g., PMX-HA, SCD) focus on "reprogramming" activated or exhausted leukocytes to restore immune homeostasis. The transition toward precision medicine in sepsis requires the integration of theragnostic biomarkers-such as mHLA-DR, NLR, and NETosis markers-to identify specific immune endotypes. Ultimately, EBP must evolve from device-agnostic applications to phenotype-driven approaches that optimize the timing and selection of extracorporeal support to improve clinical outcomes.