Interleukin-40 as a biomarker of mortality risk in patients with severe pneumonia

Severe pneumonia is an acute lung parenchyma infectious disease with a high incidence and mortality. The role of interleukin-40 (IL-40) in estimating mortality in patients with severe pneumonia remains unknown. This study aims to reveal the clinical application of IL-40 at intensive care unit (ICU) admission as a potentially novel biomarker to predict the mortality risk of severe pneumonia. Patients with severe pneumonia (n = 104), patients with non-severe pneumonia (n = 50), and healthy controls (n = 86) from May 2023 to May 2025 were enrolled. The serum IL-40 levels were measured at admission, and the 28-day survival status of the participants was compared. Furthermore, the area under the receiver operating characteristic curve (AUC) of IL-40 at ICU admission for 28-day survival was used to evaluate the ability of IL-40 in predicting the mortality of severe pneumonia. Kaplan-Meier survival curves were analyzed to evaluate the relationship between IL-40 and the mortality risk of severe pneumonia. IL-40 levels at ICU admission in patients with severe pneumonia were significantly higher than those in patients with non-severe pneumonia and healthy controls. IL-40 levels in non-survivors were significantly higher than those in survivors. The AUC of IL-40 for predicting the mortality risk of severe pneumonia was highest among the indicators. IL-40 and Sequential Organ Failure Assessment (SOFA) scores at ICU admission of patients with severe pneumonia were found to be independent predictors of 28-day mortality. The AUC of IL-40 combined with SOFA score for estimating 28-day mortality in patients with severe pneumonia increased from 0.7626 to 0.7980. Moreover, patients with severe pneumonia with higher IL-40 levels (≥1.244 ng/mL) had poorer survival than those with lower levels (<1.244 ng/mL) (p = 0.001). The IL-40 at ICU admission was valuable for predicting the mortality risk of severe pneumonia. These findings can be used as an early biomarker for early clinical decision-making in treating patients with severe pneumonia.