Leptin and Iinterlukin-6 relationship and influence of mortality in sepsis.

Abstract

Background: Sepsis is a severe and life-threatening disease involving multiple risk factors. Leptin has been suggested to play a role in modulating the inflammatory response in sepsis and improving outcomes; however, there are conflicting results regarding the outcome of sepsis. The present study aims to clarify the expression of leptin in patients with sepsis, and its association with other cytokines.

Method: The retrospective study enrolled 165 adults with sepsis from medical intensive care units (ICU)s, and collected leptin, glucose levels, and cytokines such as IL-6, IL-1RA, IL-10, IL-17, TNF-α, IFN-γfor analysis. Leptin levels were divided into three groups based on concentration: Low (≤ 3.78 ng/mL), Medium (3.78 < leptin ≤ 23.2 ng/mL), and High (> 23.2 ng/mL). Survival curve analysis and comparisons among groups were performed. A subgroup analysis by sex (male and female) was also conducted. Finally, a multiple-factor logistic regression model was used to evaluate the interaction between leptin and other factors.

Result: The high leptin groups were the oldest (low vs. medium vs. high: 60 vs. 66 vs. 78, p < 0.0001) and had the highest body mass index (BMI) (19.8 vs. 23.9 vs. 24.2, p < 0.0001), the highest percentages of women (28.6 vs. 34.1 vs. 65.9 p = 0.001), and the most comorbidities (1 vs. 1 vs. 2, p = 0.001). After controlling IL-6, day 1 leptin had a trend associated with lower mortality in the hospital (β = 0.984, p = 0.062). The highest IL-6 group had a significantly higher mortality rate among three IL-6 level patients (p = 0.015), but in the high leptin subgroup analysis, the significant effect of high IL-6 on mortality disappeared. Besides, the subgroup analysis of men, the high leptin group had a trend of better survival than the medium and low leptin groups.

Conclusion: High leptin levels may mitigate the adverse prognostic impact of elevated IL-6 on septic mortality. At comparable IL-6 levels, leptin could serve as a predictor of septic outcomes. Leptin might act as a protective factor in men. Future research should explore leptin's role in IL-6-mediated inflammation and its potential protective effect in high IL-6 sepsis cases.