Bipolar immune dynamics in sepsis: An updated perspective oscillating immunodynamics in sepsis

Sepsis remains a leading cause of global mortality and long-term morbidity. The Sepsis-3 definition shifted focus to dysregulated host responses as the primary driver of organ dysfunction. However, clinical practice often relies on static syndromic labels, overlooking the dynamic and heterogeneous immunobiology of sepsis. This review critiques linear constructs such as cytokine storm to immunoparalysis, highlighting their limitations in capturing the overlapping, fluctuating “sepsis seesaw” phenotype. We propose a translational framework emphasizing serial immune phenotyping at the bedside—combining myeloid (e.g., monocyte human leukocyte antigen-D related [mHLA-DR], etc.) and lymphoid (e.g., absolute lymphocyte count, etc.) markers, supplemented by limited gene-expression panels—to guide personalized therapeutic decisions. This approach aims to move sepsis care from uniform protocols toward precision medicine, improving patient outcomes through biology-guided interventions.