Abstract
Liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome and it is of vital importance in host defense and bacteria clearance. Our previous studies indicated that programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are crucial modulators of host immune responses during sepsis. Our current study was designed to investigate the role of PD-L1 in sepsis-induced liver injury by a mouse cecal ligation and puncture (CLP) model. Our results indicated that there was a significant increase of PD-L1 expression in liver after CLP challenge compared to sham-operated controls, in terms of levels of mRNA transcription and immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus, anti-PD-L1 antibody might have a therapeutic potential in attenuating liver injury in sepsis.
Highlights
Sepsis remains a major clinical challenge in intensive care units (ICU), characterized by the systemic inflammatory response and multiple organ failure [1]
It is accepted that liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome [8]
We examined the role of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) in 19 septic shock patients and 22 sex-matched and age-matched healthy controls
Summary
Sepsis remains a major clinical challenge in intensive care units (ICU), characterized by the systemic inflammatory response and multiple organ failure [1]. Liver is considered as the second organ affected in sepsis and liver dysfunction has been known to occur frequently in cases of sepsis [2, 3]. Sepsis-induced liver injury, as a part link of sepsis, has always been neglected by critical care physicians [4]. It is accepted that liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome [8]. Changes in hepatic metabolism occur, and they might be of vital importance in host defense and bacteria clearance [9]. Studies designed to investigate the underlying mechanisms and potential therapeutic approaches for sepsis and related organ injury are warranted
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