Endotoxin up-regulates the proinflammatory cytokines TNF-α and IL-6 in freshly-isolated human Kupffer cells
Kupffer cells, macrophages endogenous to the liver, can modulate hepatic inflammation and injury associated with various pathophysiologies and toxicities. Pro-inflammatory cytokines released by activated Kupffer cells, such as TNF-α and IL-6, are associated with up-regulation of acute-phase response proteins and suppression of CYP enzymes. For new biological entities (NBE), particularly modulators of the immune system, evaluating the potential for Kupffer cell activation is an emerging concept in preclinical development. As testing of NBE develops, robust and predictable test systems are necessary, thus the need to evaluate Kupffer cell isolation, culturing and stimulation for in vitro applications.
In the present study, Kupffer cells were isolated from non-transplantableHuman livers followed by expansion in culture and evaluation of the cytokine response to endotoxin (E. coli lipopolysaccharide, LPS).
This poster was presented at the annual ISSX meeting in 2013.