GST Mu-class Suppresses the Cytokine Storm Induced by -lipopolysaccharide Whereas Modulates the Dynamic of Peritoneal Macrophages in a Mouse Model and Suppresses the Classical Activation of Macrophages

Importance: Sepsis is an infection that can lead to a life-threatening complication. Sepsis is the consequence of a systemic bacterial infection that exacerbates the immune cells' activation by bacterial products, resulting in the augmented release of inflammatory mediators. A critical factor in the pathogenesis of sepsis is the primary component of the outer membrane of Gram-negative bacteria known as lipopolysaccharide (LPS), which is sensed by toll-like receptor 4 (TLR4). For this reason, scientists aimed to develop antagonists able to block the cytokine storm by blocking TLR4. We report here that a mixture of mu-class isoforms from the glutathione S-transferase (nFhGST) protein family administered intraperitoneally 1 h after a lethal LPS injection, is capable of significantly suppressing the LPS-induced cytokine storm in a mouse model of septic shock whereas modulate the dynamic and abundance of large peritoneal macrophages in the peritoneal cavity of septic mice. These results suggest that nFhGST is a prominent candidate for drug development against endotoxemia and other inflammatory diseases.