The Impact of Steatotic Liver Disease on Cytokine and Chemokine Kinetics During Sepsis

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been linked with sepsis outcomes. However, the immune mechanisms by which MASLD aggravates sepsis severity are unknown. This prospective cohort study aimed to analyze serum cytokine and chemokine kinetics in patients with MASLD and community-acquired sepsis. Out of the 124 patients, 68 (55%) were diagnosed with MASLD. There were no differences in age, sex, comorbidities, baseline sepsis severity, or etiology between the groups. Serum concentrations of 27 cytokines and chemokines on admission and day 5 of hospitalization were analyzed using a multiplex bead-based assay. Patients with MASLD had significantly higher serum concentrations of IL17A, IL-23, IL-33, CXCL10 and TGF-β1. Different cytokine kinetics were observed; patients with MASLD had a decrease in IL-10, IL-23, CXCL10 and TGF-β1, and an increase in IL-33, CXCL5 and CXCL1 on day 5. In the non-MASLD group, there was a decrease in IFN-γ, IL-6, IL-23 and CCL20, and an increase in CCL11 and CXCL5. While TGF-β1 significantly increased in non-MASLD, in MASLD, it decreased on day 5. Kinetics of TGF- β1 and CCL11 were associated with mortality in patients with MASLD. In conclusion, MASLD is linked with distinct cytokine and chemokine profiles during sepsis.