Immune Dysregulation in Sepsis. A Narrative Review for the Clinicians

Immune dysregulation presents a significant clinical challenge due to its rapid progression and complex interplay between hyperinflammatory and immunosuppressive responses. Different responses from the innate and adaptive immune systems can result in diseases such as immunoparalysis, cytokine storms, and secondary infections. Current diagnostic methods remain non-specific and time-consuming, delaying targeted interventions. A compartmentalized approach to immune monitoring, distinguishing innate and acquired immune response functional differentiation, is essential for distinguishing between hyperactivation and suppression. Key biomarkers, including cytokines, Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), and CD4/CD8 counts, as well as Programmed Death Ligand-1 (PDL-1) and V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) regulators, can guide personalized treatment strategies. Although they need more clinical validation, novel therapeutic methods such as cytokine inhibitors, immunological stimulants, and immunomodulators have demonstrated promise. Early diagnosis and precision medicine developments could lead to better patient outcomes. Advances in non-coding RNAs have led to specific diagnostic panels based on microRNA (MiRNA) levels. A deeper understanding of immune imbalance in sepsis is critical for optimizing treatment and reducing mortality rates. This review highlights emerging diagnostic and therapeutic strategies to address the multifaceted nature of sepsis-related immune dysregulation.