Critical Hypercytokinemia in Sepsis and Septic Shock: Identifying Interleukin-6 Thresholds Beyond Which Mortality...

Area of Science:

• Critical care medicine
• Immunology
• Biomarker research

Background:

• Patients with extremely elevated Interleukin-6 (IL-6) levels in sepsis are poorly understood.
• No established plasma concentration reliably predicts mortality or guides immunomodulatory interventions.

Purpose of the Study:

• To identify a specific Interleukin-6 (IL-6) threshold associated with significantly elevated mortality risk in patients with a hyperinflammatory sepsis endotype.
• To investigate the association between extreme hypercytokinemia and mortality in sepsis.

Main Methods:

• Retrospective, single-center observational study of adult sepsis patients (N=1669) meeting Sepsis-2 criteria.
• Analysis of plasma Interleukin-6 (IL-6) levels using cumulative conditional relative frequency and quantile-based analyses.
• Multivariable logistic regression and Kaplan-Meier survival analysis to identify predictors of mortality and IL-6 thresholds.

Main Results:

• Overall mortality was 31%. Median IL-6 was 772 pg/mL, significantly higher in non-survivors (2137 pg/mL).
• A critical IL-6 threshold of 15,000 pg/mL was identified, associated with increased mortality (OR 2.22).
• Patients with IL-6 > 15,000 pg/mL exhibited significantly reduced survival (p < 0.0001).

Conclusions:

• Plasma IL-6 levels exceeding 15,000 pg/mL define a critical threshold for increased mortality in severe sepsis or septic shock.
• Extreme hypercytokinemia (IL-6 > 15,000 pg/mL) serves as a clinically relevant biomarker for identifying high-risk patients.
• This biomarker can guide precision immunomodulatory therapies for sepsis patients with multiorgan dysfunction.