Moxibustion combined with anti-PD-1 antibodies improves immunosuppression in septic mice potentially through the PD-1/PD-L1 pathway.

This study was to investigate the therapeutic effects of moxibustion (Mox) combined with anti-PD-1 antibody on septic mice and the immune regulatory mechanism based on the PD-1/PD-L1 axis. A CLP-induced sepsis mouse model was established and intervened with moxibustion and/or anti-PD-1 antibody. It was found that both Mox and anti-PD-1 monotherapy improved mouse survival rates, reduced murine sepsis score, alleviated pathological damage in the liver, lungs, and spleen, mitigated serum biochemical abnormalities, and regulated systemic and local organ inflammation. Combination therapy demonstrated synergistic enhancement effects, yielding the most significant improvements across all metrics. Combination therapy effectively reduced intraperitoneal bacterial load and enhanced macrophage recruitment, reversed sepsis-induced decreases in spleen T cell (CD3⁺, CD4⁺, CD8⁺) proportions and CD3⁺ T cell apoptosis, corrected Th1/Th2 imbalance, and significantly downregulated PD-1 expression on spleen T cells and PD-L1 expression on neutrophils. Combination therapy suppressed PD-1, PD-L1, and STAT3 expression in the spleen while reducing STAT3 nuclear translocation. Combination therapy effectively alleviates early inflammatory storms and late-stage immunosuppression in sepsis, potentially through regulation of the PD-1/PD-L1/STAT3 signaling pathway.