Publication Date

5-2026

School

School of Health Sciences

Major

Biology: Biomedical Sciences

Keywords

Sepsis, Cytokine storm, Lymphopenia, PICS, Immune continuum, Immunoparalysis, Biomarker-guided therapy, Immune dysregulation, Precision medicine

Disciplines

Bacterial Infections and Mycoses | Diagnosis | Immune System Diseases | Other Public Health | Virus Diseases

Abstract

Sepsis is a leading cause of morbidity and mortality worldwide, driven by a dynamic immune continuum that progresses from early hyperinflammation to profound immunosuppression. This review examines the three overlapping phases of sepsis: the inflammation-mediated cytokine storm driven by dysregulated PRR activation, NF-κB signaling, and NETosis; apoptosis-driven lymphopenia involving caspase-mediated lymphocyte death, dendritic cell dysfunction, and metabolic exhaustion; and prolonged immunoparalysis culminating in persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Key mechanisms linking these phases, including the co-existence of hyper- and hypo-inflammatory states, are synthesized alongside relevant clinical biomarkers such as IL-6, HLA-DR, and single-cell immune profiles. This review highlights the need for biomarker-guided, stage-specific therapies to navigate the sepsis continuum, seeking to alleviate hyperinflammation without advancing terminal immune failure.

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