Artesunate strongly modulates myeloid and regulatory T cells to prevent LPS-induced systemic inflammation

Rubia Isler Mancuso1, Juliana Hofstätter Azambuja1, Sara Teresinha Olalla Saad1

  • 1Hematology and Transfusion Medicine Center, University of Campinas, Campinas, SP, Brazil.

Insights

Artesunate (ART) pretreatment prevents lipopolysaccharide (LPS)-induced inflammation in mice. ART treatment improved clinical scores and restored immune cell balance, reducing inflammatory markers and tissue damage.

Area of Science:

  • Immunology
  • Pharmacology
  • Microbiology

Background:

  • Lipopolysaccharide (LPS) from Gram-negative bacteria is a key inducer of inflammation.
  • Artesunate (ART), an artemisinin derivative, possesses anti-inflammatory properties.
  • Understanding ART's protective mechanisms against LPS-induced inflammation is crucial.

Purpose of the Study:

  • To investigate the efficacy of Artesunate (ART) pretreatment in preventing lipopolysaccharide (LPS)-induced inflammation.
  • To elucidate the immunomodulatory effects of ART on immune cell populations during inflammation.

Main Methods:

  • BALB/c mice were pretreated with ART (100 mg/kg) for 7 days before LPS administration.
  • Clinical scores, biochemical markers, and platelet counts were assessed.
  • Flow cytometry was used to analyze immune cell populations (macrophages, monocytes, neutrophils, MDSC, T cells) in bone marrow, spleen, and peripheral blood.
  • Inflammatory cytokines and chemokines were quantified.

Main Results:

  • ART pretreatment significantly improved clinical scores and normalized biochemical markers and platelet counts.
  • ART modulated macrophage polarization, reducing M1 and increasing M2 macrophages.
  • ART increased regulatory T cells, myeloid-derived suppressor cells (MDSC), and N2 neutrophils in immune organs and peripheral blood.
  • ART treatment markedly decreased levels of inflammatory cytokines and chemokines.

Conclusions:

  • Artesunate (ART) effectively prevents LPS-induced inflammation by modulating immune cell responses.
  • ART treatment restores immune homeostasis, reduces tissue damage, and mitigates inflammatory responses.
  • ART demonstrates potential as a therapeutic agent for inflammatory conditions.