Melatonin Inhibits CD4+T Cell Apoptosis via the Bcl‐2/BAX Pathway and Improves Survival Rates in Mice With Sepsis

This study examined whether melatonin could decrease CD4 + T cell apoptosis and reduce mortality rates in sepsis‐induced mice. Fifty‐one male C57BL/6 mice were randomly classified into three groups: Sham, cecal ligation and puncture (CLP), and CLP plus melatonin (CLP + MLT). Mice in the CLP + MLT group were intraperitoneally administered melatonin at 30 mg/kg 10 min before and 30 min after CLP and then once daily for 6 days. Lymphocyte counts, cytokine levels, and apoptosis rates in CD4+ and CD8 + T cells in the spleen and peripheral blood were examined using automatic blood cell analysis, enzyme‐linked immunosorbent assay, or flow cytometry. The results demonstrated that melatonin improved the survival of mice following CLP, decreased the levels of IFN‐γ, IL‐1β, and IL‐2 in the serum, and significantly upregulated lymphocyte counts. In addition, melatonin increased the percentage of CD4 + T cells and inhibited the apoptosis of these cells in the spleen and peripheral blood of mice following CLP. Melatonin protected against sepsis‐induced organ damage. Melatonin inhibited CD4 + T cell apoptosis in vitro, possibly via the Bcl‐2/BAX but not through the PD‐1 pathway. Our results suggest that melatonin could mitigate Pro‐inflammatory responses, attenuate organ injury, and suppress CD4 + T cell apoptosis via the Bcl‐2/BAX pathway, thereby improving survival rates in a mouse model of sepsis. Targeted therapy to protect CD4 + T cells against apoptosis could represent a new approach for sepsis treatment in the future.