To assess the role of lactate as an epigenetic mediator influencing immune dysfunction in diabetic sepsis and its implications for treatment.
Key Findings:
Diabetic sepsis patients show elevated inflammatory cytokines and impaired antigen presentation, leading to higher mortality rates compared to non-diabetic patients.
Lactate levels rise significantly during sepsis, with hyperlactataemia linked to immune dysfunction via GPR81 receptor activation and histone lactylation, highlighting the need for further exploration.
Histone lactylation at H3K18 selectively activates inflammatory genes while suppressing antigen presentation pathways, providing a molecular basis for the paradox of inflammation and immunosuppression.
Preliminary studies indicate a correlation between H3K18la levels and disease severity, with lactate clearance <30% in 6 hours associated with poor prognosis, underscoring the urgency for targeted interventions.
Interpretation:
Lactate acts as both a metabolic marker and an active signaling molecule that modulates immune responses in diabetic sepsis, contributing to the paradox of inflammation and immunosuppression, with significant implications for treatment strategies.
Limitations:
Current therapeutic evidence is limited and lacks proven survival benefits, necessitating caution in clinical application.
Existing studies are fragmented and require systematic exploration and validation to establish a comprehensive understanding.
Conclusion:
The review identifies potential therapeutic targets for diabetic sepsis, including metabolic regulation, intervention in the GPR81-H3K18la axis, and personalized therapy based on immune phenotypes, necessitating urgent further clinical trials.
