Combination therapy with probiotics and anti-PD-L1 antibody synergistically ameliorates sepsis in mouse model

The study investigated the protective effects and mechanisms of probiotics in conjunction with an anti-PD-L1 antibody on the immune functions of septic mice. Sixty-four mice were assigned to sepsis groups receiving vehicle, probiotics, and anti-PD-L1 antibody individually or in combination, with healthy mice as controls. Sepsis was induced by cecal ligation and puncture (CLP), followed by intraperitoneal Lipopolysaccharide (LPS) injection. Blood and tissues were collected one day post-injection for detecting inflammation-related cytokines, Treg, PI3K/Akt pathway-related protein expression, and lung tissue pathology. The survival time of the remaining ten mice was recorded over seven days. Compared to healthy mice, septic mice given PBS exhibited significantly different serum levels of IL-6, IL-8, IL-17, IL-10, and IFN-γ (all p < 0.001). Treatment with anti-PD-L1 antibody combined with probiotics significantly increased the 7-day survival rate in septic mice, accompanied by decreased pro-inflammatory cytokines, increased anti-inflammatory cytokines, improved oxidative stress, reduced lung injury, and enhanced Th17/Treg balance. This combined therapy demonstrated superior efficacy compared to antibodies or probiotics alone. Additionally, it facilitated peripheral blood polymorphonuclear neutrophil apoptosis, enhancing protection by blocking PD-L1 function and inhibiting PI3K-dependent AKT phosphorylation. In conclusion, combining probiotics with an anti-PD-L1 antibody enhances protective effects in septic mice by reducing serum inflammatory factors, promoting neutrophil apoptosis, regulating Th17/Treg balance, and inhibiting the PI3K/Akt pathway.