Interleukin-37 as a biomarker of mortality risk in patients with sepsis

Abstract

Background: Sepsis is a serious syndrome that is caused by an unbalanced inflammatory response to infection and can cause high mortality. The role of interleukin-37 (IL-37) in estimating the mortality in patients with sepsis remains unknown. This study aims to reveal the clinical application of IL-37 as a potentially novel biomarker to predict mortality risk in patients with sepsis.

Methods: The serum IL-37 level in 114 adult septic patient serum samples on the day of intensive care unit (ICU) admission, 56 non-sepsis ICU patients, and 56 healthy volunteers were measured and analyzed, and the 28-day survival status and sequential organ failure assessment (SOFA) scores of the participants were compared. Furthermore, the area under the receiver operating characteristic curve (AUC) of IL-37, IL-6, and SOFA at ICU admission for 28-day survival was used to evaluate the ability of IL-37 in predicting the mortality of sepsis.

Results: The serum IL-37 level at admission was elevated in patients with sepsis. Moreover, the concentration of IL-37 in patients with sepsis was significantly higher than that in non-sepsis ICU patients and the healthy control group. In addition, the concentration of serum IL-37 in non-surviving patients with sepsis was significantly higher than that in survivors. In patients with sepsis on the day of ICU admission, the AUC associated with 28-day mortality was 0.67 (p = 0.0022;95% confidence interval [95% CI], 0.57-0.77) for IL-37, 0.75 (p < 0.0001; 95% CI, 0.66-0.84) for SOFA, and 0.62 (p = 0.0342; 95% CI, 0.51-0.72) for IL-6. IL-37 and SOFA scores on the day of ICU admission of the patients with sepsis were found to be independent predictors of 28-day mortality, whereas IL-6 was not. The risk of mortality in patients with sepsis and high serum IL-37 concentration (≥107.05pg/ml) was 4.6 times that of patients with sepsis and low serum concentration. The AUC of IL-37 combined with SOFA-estimated 28-day mortality in patients with sepsis increased from 0.67 (p = 0.0022; 95% CI, 0.57-0.77) to 0.80 (p < 0.0001; 95% CI, 0.711-0.879). In addition, patients with sepsis and high serum IL-37 concentrations (≥107.05pg/ml) had poorer survival rate than those with low serum concentrations (<107.05pg/ml).

Conclusion: IL-37 concentrations at ICU admission are valuable for predicting the 28-day mortality risk of patients with sepsis, suggesting that IL-37 may be a novel biomarker. These findings can be used as a basis for guiding early clinical decision-making in treating patients with sepsis.

Keywords: Biomarker; IL-37; Interleukin-6 (IL-6); Mortality; Procalcitonin (PCT); SOFA score; Sepsis.