Novel Insights for Systemic Inflammation in Sepsis and Hemorrhage

Figure 2

Inflammatory response of HMGB1 and its attenuation by ethyl pyruvate. HMGB1 is liberated from macrophages into the extracellular milieu following cell membrane perturbations during sepses, hemorrhage, and injury. HMGB1-mediated nitric oxide (NO) leakages the endothelial line leading to a high permeability. NFKB signally stimulated by HMGB1 in macrophage regulates the release of TNF cytokine and interleukins. Inflammatory shock and animal death result due to vascular collapse and cytokine toxicity of the organ tissues. By attenuating the HMGB1 pathways with hextend-ethyl pyruvate (HEP), animals may improve survival with the dependent dosage.