Causal Relationships Between Inflammatory Cytokines and Sepsis: A Mendelian Randomization Study

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Epidemiology

Background:

• The relationship between inflammatory cytokines and sepsis is complex and not fully understood.
• Identifying causal factors is crucial for developing effective sepsis treatments.

Purpose of the Study:

• To investigate the causal relationships between inflammatory cytokines and sepsis using Mendelian Randomization (MR).
• To identify potential therapeutic targets for sepsis by elucidating cytokine involvement.

Main Methods:

• Employed a bidirectional Mendelian Randomization (MR) approach.
• Utilized genetic variants from genome-wide association studies (GWAS) as instrumental variables.
• Applied Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median methods, with stringent SNP filtering and pleiotropy checks (MR-PRESSO).

Main Results:

• CTACK, MIF, and TRAIL were identified as risk factors for sepsis.
• MIP1-β and TGF-α demonstrated a protective effect against sepsis.
• Sepsis was found to increase risk for IL-2, IL-6, and MCSF, while protectively affecting NGF-β and SCF.

Conclusions:

• Established novel causal links between specific inflammatory cytokines and sepsis.
• Highlighted the bidirectional nature of interactions between sepsis and cytokine profiles.
• Provided insights for targeted therapeutic strategies for sepsis management.