Infectious disease

Cell culture and mouse studies suggest inhibiting PKM2 could help treat sepsis. In lipopolysaccharide (LPS)-pretreated mouse bone marrow-derived macrophages and a human monocytic cell line, PKM2 knockdown or a PKM2 inhibitor tool compound decreased inflammasome activation - a marker of sepsis - compared with normal PKM2 expression or vehicle. In two mouse models of sepsis, two PKM2 inhibitor tool compounds decreased activity of the inflammasome marker caspase-1 (CASP1) in peritoneal macrophages, and one of the inhibitors increased survival compared with vehicle. Next steps include identifying and testing PKM2 inhibitors in additional models of sepsis...