Molecular Pathways in Sepsis Pathogenesis: Recent Advances and Therapeutic Avenues

Background: Sepsis remains a critical global health challenge with high mortality. This review summarizes current understanding of the intricate molecular mechanisms governing sepsis pathogenesis and highlights emerging therapeutic approaches.

Main body of the abstract: The dysregulated immune response in sepsis, involving both excessive inflammation and immunosuppression, is mediated through cytokines, pattern recognition receptors, and disturbances in immune cell function. Endothelial dysfunction, coagulation abnormalities, microbiome dysbiosis, and metabolic/mitochondrial alterations also critically contribute to sepsis progression. Preclinical models have facilitated detailed study of these pathways and identification of potential therapeutic targets, including immunomodulators, microbiome-directed therapies, endothelial modulators, anticoagulants, and metabolic/mitochondrial agents. Combination therapies targeting multiple pathogenic aspects may be necessary. However, translating preclinical findings to clinical applications remains challenging. Heterogeneity among sepsis patients is a key issue, underscoring the need for precision medicine approaches. Potential adverse effects and optimal treatment regimens must be rigorously evaluated.

Short conclusion: Further research should focus on validating preclinical discoveries, understanding sepsis subtypes, developing predictive biomarkers and innovative therapies including artificial intelligence-based tools, and bridging knowledge gaps through enhanced academia-industry collaboration. Comprehensive efforts spanning from unraveling molecular pathways to clinical translation hold promise for improving outcomes in this deadly syndrome.