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Published on: July 26, 2017
Therapeutic strategies targeting the LPS signaling and cytokines
Hua-Dong Wang1, Da-Xiang Lu, Ren-Bin Qi
1Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, China.
Abstract:
Lipopolysaccharide (LPS) has been recognized as a major player in the pathogenesis of sepsis and neutralization of LPS or inhibition of its signal transduction mechanism is promising new treatment strategy in preclinical experiments. However, these therapeutic approaches have been shown unsuccessful in clinical trials. LPS activates Toll-like receptor 4 (TLR4) and induces pro-inflammatory and anti-inflammatory responses, the altered innate and adaptive immune responses eventually lead to the immunosuppressive state. The future therapeutic efforts in sepsis should focus on the immunosuppressive state. In this article, we will outline the current data on therapeutic strategies targeting LPS, TLR4 and single cytokine in sepsis and discuss the experimental and clinical evaluation of the immunomodulatory action of glycine and berberine. While we have demonstrated berberine in combination with yohimbine can modulate host immune responses in endotoxemia, it seems worthwhile to conduct clinical trials on the safe and efficacy of this new immunomodulatory therapy.
Insights
Lipopolysaccharide (LPS) triggers sepsis but targeting it failed clinically. Future sepsis treatments should address the resulting immunosuppression, potentially using agents like glycine and berberine.
Area of Science:
- Immunology
- Pharmacology
- Sepsis Pathogenesis
Background:
- Lipopolysaccharide (LPS) is a key factor in sepsis development.
- Therapies targeting LPS or its signaling pathway (Toll-like receptor 4 - TLR4) have shown promise preclinically but failed in clinical trials.
- Sepsis involves complex immune dysregulation, leading to an immunosuppressive state.
Purpose of the Study:
- To review current therapeutic strategies for sepsis targeting LPS, TLR4, and cytokines.
- To discuss the immunomodulatory effects of glycine and berberine in sepsis.
- To evaluate the potential of novel immunomodulatory therapies for sepsis.
Main Methods:
- Review of preclinical and clinical data on sepsis therapeutics.
- Experimental evaluation of glycine and berberine's immunomodulatory actions.
- Analysis of host immune response modulation in endotoxemia.
Main Results:
- Targeting LPS and TLR4 has been clinically unsuccessful.
- Sepsis leads to an immunosuppressive state that warrants therapeutic focus.
- Berberine combined with yohimbine demonstrated immune response modulation in endotoxemia.
Conclusions:
- Future sepsis therapies should target the immunosuppressive state.
- Glycine and berberine show potential as immunomodulatory agents.
- Clinical trials are recommended for berberine and yohimbine combination therapy for sepsis.
