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Subcutaneous Infection of Methicillin Resistant Staphylococcus Aureus MRSA
Published on: February 9, 2011
Xuebijing Injection Alleviates Pam3CSK4-Induced Inflammatory Response and Protects Mice From Sepsis Caused by
Tiantian Li1, Yiming Qian2, Zhulei Miao1
1Department of Immunology and Microbiology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Abstract:
A leading cause of death worldwide is sepsis that develops as a dysregulated immune response to infection. Serious infection caused by methicillin-resistant Staphylococcus aureus (MRSA) increases the difficulty of treatment in septic patients. Host-directed therapy (HDT) is an emerging approach to bacterial infections. Xuebijing injection (XBJ), a commercialized injectable prescription from traditional Chinese medicine, has been used as adjuvant therapy for sepsis with a history of 15 years. Whether it plays a protective role in severe infection caused by antibiotic-resistant bacteria is still unknown. In this study, XBJ significantly improved the survival of MRSA-induced sepsis mice. In MRSA-infected mouse model, XBJ down-regulated the expression of inflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, MCP-1, MIP-2, and IL-10 in sera. Besides that, it decreased the bacterial load in spleens, livers, and alleviated tissue damage of lung, liver, and kidney. The combination of XBJ with vancomycin or dexamethasone exhibited a better down-regulatory role of the inflammatory response. Then, the protective mechanism of XBJ was further investigated. XBJ inhibited heat-killed MRSA-induced IL-6 and TNF-α production in mouse macrophages. XBJ also decreased Pam3CSK4 (a synthetic tripalmitoylated lipopeptide mimicking bacterial lipoproteins)-stimulated expression of IL-6, TNF-α, IL-1β, IL-12, etc. in mouse macrophages. Furthermore, XBJ down-regulated the activation of NF-κB, MAPK, and PI3K/Akt pathways in Pam3CSK4-stimulated mouse macrophages. In conclusion, our findings demonstrated that XBJ played a protective role in MRSA-challenged mice and down-regulated the inflammatory response and the activation of signaling pathways initiated by Pam3CSK4. It enlarged the clinical application of XBJ in the treatment of severe bacterial infection, e.g. caused by MRSA.
Insights
Xuebijing injection (XBJ) improves survival in mice with methicillin-resistant Staphylococcus aureus (MRSA) sepsis. This traditional Chinese medicine reduces inflammation and bacterial load, offering potential for treating antibiotic-resistant infections.
Area of Science:
- Immunology
- Pharmacology
- Traditional Chinese Medicine
Background:
- Sepsis is a leading global cause of death, often complicated by antibiotic-resistant bacteria like MRSA.
- Host-directed therapy (HDT) is an emerging strategy for bacterial infections.
- Xuebijing injection (XBJ), a traditional Chinese medicine, is used as adjuvant sepsis therapy, but its efficacy against antibiotic-resistant bacteria is unclear.
Purpose of the Study:
- To investigate the protective role of XBJ in a mouse model of MRSA-induced sepsis.
- To elucidate the underlying mechanisms of XBJ's therapeutic effects.
Main Methods:
- Established a mouse model of MRSA-induced sepsis.
- Administered XBJ and assessed survival rates, inflammatory cytokine levels (IL-6, TNF-α, etc.), bacterial load, and tissue damage.
- Investigated XBJ's effects on inflammatory cytokine production and signaling pathways (NF-κB, MAPK, PI3K/Akt) in mouse macrophages stimulated with heat-killed MRSA or Pam3CSK4.
Main Results:
- XBJ significantly improved survival in MRSA-sepsis mice.
- XBJ down-regulated serum inflammatory cytokines, reduced bacterial load in organs, and alleviated tissue damage.
- XBJ inhibited MRSA- or Pam3CSK4-induced inflammatory cytokine production in macrophages and suppressed NF-κB, MAPK, and PI3K/Akt pathway activation.
Conclusions:
- XBJ demonstrates a protective effect against MRSA-induced sepsis in mice.
- XBJ exerts its therapeutic benefits by modulating inflammatory responses and inhibiting key signaling pathways.
- These findings support the expanded clinical application of XBJ for severe bacterial infections, including those caused by MRSA.

