Which cytokine can be used as a prognostic marker in sepsis, Interleukin (IL)-6?

Interleukin-6 (IL-6) is the Most Valuable Cytokine Prognostic Marker in Sepsis

The correct answer is (c) interleukin-6, which has been consistently demonstrated to be the most valuable cytokine for prognostic assessment in sepsis patients.

Evidence Supporting IL-6 as a Prognostic Marker

• Elevated IL-6 levels are significantly correlated with sepsis severity, development of septic shock, and mortality, making it superior to other cytokines for prognostic assessment 1, 2.

• IL-6 levels can distinguish between sepsis and septic shock with high sensitivity (76.1%) and specificity (78.4%) at a cut-off value of 348.92 pg/mL 2.

• High IL-6 levels (≥348.92 pg/mL) are independently associated with increased 28-day mortality in sepsis patients (hazard ratio 1.0004,95% CI 1.0003-1.0005, p=0.024) 2.

• In patients with septic shock, IL-6 levels can be up to 7,500 times normal levels, with the highest levels found in non-survivors compared to survivors (p<0.0001) 3.

Clinical Correlation with Disease Severity

• IL-6 levels strongly correlate with important clinical parameters:

  • Plasma lactate levels (p<0.0001) 3
  • Heart rate (p=0.05) 3
  • Mean arterial pressure (inverse correlation, p=0.01) 3
  • Platelet counts (inverse correlation, p=0.0002) 3

• IL-6 shows strong positive correlation with established severity scores:

  • APACHE II scores (r=0.72; p<0.001) 4
  • SOFA scores (r=0.68; p<0.001) 4

Predictive Value for Complications

• Elevated IL-6 levels predict development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS) in sepsis patients 4.

• Patients who develop ALI have significantly higher IL-6 levels than those without ALI (median: 125.6 pg/mL vs 48.3 pg/mL; p<0.001) 4.

• Similarly, patients with MODS show higher IL-6 levels than those without MODS (median: 142.9 pg/mL vs 58.7 pg/mL; p<0.001) 4.

Temporal Changes in IL-6 and Survival

• The pattern of IL-6 levels over time has prognostic significance - patients with sepsis who survive show a significant decline in IL-6 levels within 48 hours of admission 5.

• In contrast, persistently elevated IL-6 levels in septic shock patients correlate with lower survival rates - only 25% of septic shock patients with persistently high IL-6 levels survive beyond 15 days (p=0.005) 5.

Diagnostic Value

• IL-6 is an independent predictor for sepsis diagnosis, with an area under the curve (AUC) of 0.764 6.

• When combined with other markers (BUN and MAP), the diagnostic accuracy improves significantly (AUC 0.848) 6.

Limitations and Considerations

• While IL-6 has strong prognostic value, there is still a need for standardization of cut-off values, which range widely from 12 to 2760 pg/mL across different studies 7.

• Some guidelines note that inflammatory biomarkers including IL-6 require further controlled studies before their measurement can definitively guide clinical care of critically ill patients 7.

Comparison with Other Cytokines

• The diagnostic and prognostic value of IL-6 has been shown to be superior to other inflammatory markers including procalcitonin (PCT) and pentraxin 3 (PTX3) for sepsis and septic shock 2.

• While TNF-α, IL-1, IL-2, and IL-8 are also found in sepsis patients, they have not demonstrated the same consistent prognostic value as IL-6 1.