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

  • Transpl Immunol. 2025 May:90:102217. doi: 10.1016/j.trim.2025.102217.
Haoran Tang  1 ,  Chen Liao  1 ,  Lingling Wang  2 ,  Wei Fang  3 ,  Ning Tang  4 ,  Linjun Wan  5 ,  Zongfang Ren  6
Affiliations
  • 1. Department of Gastroenterological Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 2. Department of Medical Intensive Care Unit, General Hospital of Southern Theater Command of PLA, Guangzhou, China.
  • 3. Department of Medical Intensive Care Unit, CiHui Hospital, Guangzhou, China.
  • 4. Department of Neurology, The First People's Hospital of Yunnan Province, Kunming University of Science and Technology, Kunming, China.
  • 5. Department of Critical Care Medicine, the Second Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
  • 6. Department of Critical Care Medicine, the Second Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: [email protected].
PMID: 40107628 DOI: 10.1016/j.trim.2025.102217
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.

Keywords
Immunosuppression; Myeloid-derived suppressor cell; NF-κB; Sepsis; Swertianolin.
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