Inflammation-driven multiorgan Dysfunction: Biomarker-Guided diagnosis, mechanistic insights and emerging precision therapeutic strategies

Inflammation-driven multiorgan dysfunction syndrome (MODS) represents a major cause of morbidity and mortality in critically ill patients and arises from a complex interplay of dysregulated immune responses, endothelial injury, microvascular dysfunction, metabolic disturbances, and maladaptive organ crosstalk. Although traditionally associated with sepsis, similar inflammatory pathways contribute to organ dysfunction in trauma, pancreatitis, severe viral infections, autoimmune disorders, and other critical illnesses. This review synthesizes current evidence regarding the molecular and cellular mechanisms underlying inflammation-driven MODS, with particular emphasis on cytokine amplification, innate and adaptive immune dysregulation, immunothrombosis, oxidative stress, mitochondrial dysfunction, and barrier failure across multiple organ systems. Emerging biomarkers, including inflammatory cytokines, endothelial injury markers, damage-associated molecular patterns, and organ-specific indicators, are discussed for their diagnostic, prognostic, and therapeutic relevance. However, significant challenges remain, including biomarker variability, lack of standardized thresholds, and the absence of universally accepted diagnostic panels for routine clinical use. The review further examines organ-specific manifestations and evolving therapeutic strategies, including anti-cytokine therapies, immunomodulation, endothelial protection, extracorporeal blood purification, and metabolic-targeted interventions. Importantly, many promising anti-inflammatory therapies have demonstrated limited success in clinical translation due to patient heterogeneity, inappropriate timing of intervention, and the dynamic transition between hyperinflammatory and immunosuppressed states. Advances in precision medicine and artificial intelligence offer opportunities for individualized risk stratification and biomarker-guided treatment selection, supporting improved health outcomes, quality of life, healthcare innovation, and sustainable healthcare systems. Integrating biomarker-driven insights with mechanistic understanding may improve clinical outcomes, reduce mortality, and facilitate the development of targeted therapies for this complex syndrome. Addressing these challenges will be essential for developing phenotype-driven therapeutic approaches and improving outcomes in patients with inflammation-driven multiorgan dysfunction.