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

Area of Science:

• Immunology
• Pharmacology
• Sepsis Research

Background:

• Sepsis is a life-threatening condition characterized by dysregulated immune response.
• T cell apoptosis contributes to immune dysfunction and mortality in sepsis.
• Melatonin, a hormone with antioxidant and anti-inflammatory properties, has shown potential in various disease models.

Purpose of the Study:

• To investigate the protective effects of melatonin on CD4+ T cell apoptosis and survival rates in a mouse model of sepsis.
• To elucidate the molecular mechanisms underlying melatonin's action on T cells in sepsis.

Main Methods:

• Cecal ligation and puncture (CLP) model in male C57BL/6 mice.
• Administration of melatonin (30 mg/kg) to CLP mice.
• Assessment of survival rates, lymphocyte counts, cytokine levels (IFN-γ, IL-1β, IL-2), and CD4+/CD8+ T cell apoptosis via flow cytometry and ELISA.
• In vitro studies to explore the role of Bcl-2/BAX and PD-1 pathways.

Main Results:

• Melatonin significantly improved survival rates in CLP mice.
• Melatonin reduced pro-inflammatory cytokine levels (IFN-γ, IL-1β, IL-2) and increased lymphocyte counts.
• Melatonin inhibited CD4+ T cell apoptosis in spleen and peripheral blood, potentially via the Bcl-2/BAX pathway.
• Melatonin treatment protected against sepsis-induced organ damage.

Conclusions:

• Melatonin mitigates sepsis-induced inflammation and organ injury by suppressing CD4+ T cell apoptosis through the Bcl-2/BAX pathway.
• Melatonin enhances survival in a sepsis mouse model, highlighting its therapeutic potential.
• Targeting CD4+ T cell apoptosis represents a promising future strategy for sepsis treatment.