Abstract

Background: Immunosuppression in sepsis is hypothesized to result from the increased expression of the immune checkpoint molecules programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1). PD-1 and PD-L1 blockade therapies have been reported to increase survival in septic animals. Currently, the interleukin (IL)-10 within mesenchymal stem cell (MSC) secretome is known for its immunomodulatory capacity. Objective: To study the effect of IL-10 within MSC secretome on the expression of immune checkpoints in the rat model of sepsis. Methods: We used 48 male Rattus norvegicus rats in this research and divided them into four groups: sham (rats without sepsis induction and treatment), control (sepsis-induced rats without treatment), T1 (sepsis-induced rats treated with 150 µL of secreted IL-10 from MSC), and T2 (sepsis-induced rats treated with 300 µL of secreted IL-10 from MSC). Forty-eight hours after sepsis induction, we terminated the rats and collected the blood to examine the PD-1 and PD-L1 expression levels. Results: We found a decrease in the relative expression of PD-1 in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group, but the decrease was not significant. We also found a decrease in the relative expression of PD-L1 mRNA in the septic rat group given 150 µL and 300 µL of secreted IL-10 from MSC compared to the control group. Conclusion: Administering secreted IL-10 from MSC reduces the expression of PD-1 and PD-L1 in sepsis. These findings suggest that MSC secretome can improve the immunosuppression in sepsis.

Key words: IL-10, immune checkpoints, immunosuppression, secretome, sepsis.