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Published on: September 12, 2016
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.
Abstract:
Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria and is usually administrated to establish models of inflammation. Artesunate (ART), a water-soluble artemisinin derivative, displays multiple pharmacological actions against tumors, viral infections, and inflammation, and has been used as a therapeutic weapon against malaria. In this study, our aim was to evaluate whether ART pretreatment is capable of preventing inflammation induced by LPS. BALB/c mice were treated with 100 mg/kg of ART i.p. for 7 days followed by a single dose of LPS. ART pretreatment led to an improvement in clinical score, prevented alterations in biochemical markers, and reestablished the platelet counts. Flow cytometry analysis showed that ART protected the inflammation mainly by reducing the percentage of M1 macrophages while increasing M2 macrophages and a reestablishment of classical monocytes in the BM. In the spleen, ART pretreatment increased N2 neutrophils, myeloid-derived suppressor cells (MDSC), and regulatory T cells, the latter was also increased in peripheral blood. In addition, a marked decrease in inflammatory cytokines and chemokines was observed in the ART treated group. Our data suggest that ART prevents inflammation, reducing tissue damage and restoring homeostasis.
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.

