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.