IL-35 is elevated in clinical and experimental sepsis and mediates inflammation

•IL-35 increase occurred in sepsis irrespective of patient age and the primary source of infection.•Serum IL-35 was strongly associated with markers of systemic inflammation and disease severity.•Administration of anti-IL-35 p35 antibodies significantly diminished dissemination of the bacteria in septic animals.

Sepsis carries considerable morbidity and mortality. IL-35 is a newly described cytokine, which plays a regulatory role in infection and immunity. In this study, we found that IL-35 concentration in serum samples from adult or child patients with sepsis was significantly higher compared with that from healthy controls. IL-35 gradually increased according to sepsis severity. Increased serum IL-35 was associated with LOD (Logistic Organ Dysfunction) or SAPS II (Simplified Acute Physiology Score) scores, and correlated with markers of inflammation. In murine abdominal sepsis, administration of anti-IL-35 p35 antibodies significantly diminished dissemination of the bacteria in septic animals, which was accompanied by enhanced local neutrophil recruitment and early increased release of inflammatory cytokines and chemokines. Therefore, sepsis is associated with enhanced release of IL-35. In abdominal sepsis, IL-35 likely facilitates bacterial dissemination. IL-35 plays a major role in the immunopathogenesis of sepsis.