Sepsis is life-threatening organ dysfunction caused by a dysregulated host response in which hyperinflammation and counter-regulatory immunosuppression often coexist and shift over time. Interleukin-10 (IL-10) is a central immunoregulatory cytokine in this balance. Early IL-10 signaling can restrain innate cytokine amplification, limit tissue injury, and promote tolerance; however, sustained or context-mismatched IL-10 impairs antigen presentation and antimicrobial effector functions, contributing to sepsis-associated immunoparalysis, secondary infections, and poor outcomes. We summarize the cellular sources and multilayer regulation of IL-10 in sepsis, spanning transcriptional programs, cytokine circuits, and immunometabolic remodeling. Clinically, IL-10 is rarely informative as a standalone biomarker; its utility increases when interpreted longitudinally and integrated with immune-function readouts (e.g., lymphocyte indices, monocyte HLA-DR) and broader biomarker patterns to assign host-response endotypes. We then review IL-10–linked therapeutic strategies and propose an IL-10-aware precision framework that connects biomarker trajectories to endotype-aligned treatment windows, safety guardrails, and adaptive trial designs. Integrating mechanistic insight with dynamic stratification may enable more effective, individualized host-directed interventions in sepsis.
Wang et al. (Wed,) studied this question.