Sterile inflammation in liver transplantation

Abstract

Sterile inflammation is the immune response to damage-associated molecular patterns (DAMPs) released during cell death in the absence of foreign pathogens. In the setting of solid organ transplantation, ischemia-reperfusion injury results in mitochondria-mediated production of reactive oxygen and nitrogen species that are a major cause of uncontrolled cell death and release of various DAMPs from the graft tissue. When properly regulated, the immune response initiated by DAMP-sensing serves as means of damage control and is necessary for initiation of recovery pathways and re-establishment of homeostasis. In contrast, a dysregulated or overt sterile inflammatory response can inadvertently lead to further injury through recruitment of immune cells, innate immune cell activation, and sensitization of the adaptive immune system. In liver transplantation, sterile inflammation may manifest as early graft dysfunction, acute graft failure, or increased risk of immunosuppression-resistant rejection. Understanding the mechanisms of the development of sterile inflammation in the setting of liver transplantation is crucial for finding reliable biomarkers that predict graft function, and for development of therapeutic approaches to improve long-term transplant outcomes. Here, we discuss the recent advances that have been made to elucidate the early signs of sterile inflammation and extent of damage from it. We also discuss new therapeutics that may be effective in quelling the detrimental effects of sterile inflammation.

An integrated proteomics and metabolomics approach to assess graft quality and predict early allograft dysfunction after liver transplantation: a retrospective cohort study

“… 63 performed proteomics analysis in a liver graft and found significantly differential expressed proteins, which were related to immune and inflammatory responses, host defense, and neutrophil degranulation, between the acute kidney injury group and the non-acute kidney injury group. Therefore, a more severe graft inflammation status, possibly as a consequence of donation after circulatory death (DCD), steatosis, or long-distance traveling liver graft, would be associated with poor organ function after LT. Strategies aiming to alleviate sterile inflammation such as pharmacological therapies and machine perfusion have been developed to preserve organ function and improve long-term transplant outcomes, particularly for expanded criteria donors like DCD 64 .…”

Nepetoidin B Alleviates Liver Ischemia/Reperfusion Injury via Regulating MKP5 and JNK/P38 Pathway

“…Studies have indicated that liver I/R injury is characterized by an increase in inflammatory factors and apoptosis. 22 The liver defense against I/R-induced damage can be achieved by inhibiting inflammatory and apoptosis-related signaling. Liu et al showed that cordycepin attenuates liver I/R injury by inhibiting apoptosis and inflammatory responses.…”