Therapeutic strategies targeting the LPS signaling and cytokines

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.