Swertianolin regulates immunosuppression of myeloid suppressor cells in septic mice by inhibiting NF-κB and P38 signaling.

Abstract

Background: Swertianolin is one of the main components of Gentianaceae Swertia plants, a traditional Chinese medicine used for the treatment of infection, fever, viral hepatitis, and pneumonia. An expansion of myeloid-derived suppressor cells (MDSCs) contributes to sepsis induced immunosuppression. We investigated the mechanism by which Swertianolin regulates MDSCs in a mouse model of sepsis.

Methods: Severe sepsis was induced in mice using caecal ligation and puncture. These mice received an intraperitoneal injection of Swertianolin. MDSCs were isolated and analyzed by flow cytometry; serum concentrations of immunosuppressive factors were detected by ELISA; and mitogen-activated protein kinase and nuclear factor-κB (NFκB) were detected by Western blots.

Results: We found that Swertianolin reduced the number of MDSCs in the marrow and the spleen while increased the number of CD4+ T cells in the spleen of mice with sepsis in comparison to controls (p < 0.05). Swertianolin reduced lung damage and improved the survival rate in mice with secondary infection of Legionella pneumophila (p < 0.05). Swertianolin inhibited the phosphorylation of p38 and nuclear translocation of p65 in MDSCs (p < 0.05), leading to decreased production of IL-10 and nitric oxide (both p < 0.05).

Conclusion: Swertianolin may improve immunosuppressive function of MDSCs and increased T cell activity by inhibiting p38 phosphorylation and NF-κB activation.