Ouabain Attenuates Sepsis-Induced Immunosuppression in Mice by Activation and Anti-Apoptosis of T Cells
Ruibin Niu, Hao Gao, Yuan Zhou, Jie Zhang
Department of Anesthesiology, Huashan Hospital North Affiliated to Fudan University, Shanghai, China (mainland)
Med Sci Monit 2018; 24:2720-2727
Sepsis is known to trigger impaired T cell function, which relates to immunosuppression, contributing to refractory infection and high mortality. The mechanisms of T cell recovery remain to be elucidated, and novel and effective therapeutics for sepsis are needed. Ouabain, a small molecule of cardiac glycosides, can reverse immunoparalysis in many settings.
MATERIAL AND METHODS: Our study was designed to determine if ouabain can relieve sepsis by modulating T cell response and related pathways. The “two-hit” model of sepsis was applied, established by intraperitoneally LPS injection 3 days after cecal ligation puncture (CLP-LPS). Ouabain was administered to mice intravenously (0.1 mg/kg) after in vivo LPS stimulation every day for 4 days. The survival rate of mice, level of serum cytokines, percentage of activated T cells, apoptosis of T cells, and possibly related genes were assessed.
RESULTS: The results suggest that ouabain administration after establishment of the CLP-LPS model improved survival rates, elevated pro-inflammatory cytokines, and decreased anti-inflammatory cytokines in serum. More activated T cells and fewer apoptotic T cells were detected in the spleens after treatment with ouabain. Such changes might correlate with the genes of Bcl-2, PUMA, IRAK-M, and SOCS1.
CONCLUSIONS: Taken together, our data show ouabain is a T cell mediator during sepsis recovery.
Keywords: Immunosuppression, Ouabain, Sepsis