Modulation of monocyte/macrophage function: a therapeutic strategy in the treatment of acute liver failure.
Acute liver failure (ALF) is a condition with a high mortality and morbidity for which new treatments are desperately required. We contend that although the initial event in ALF is liver cell death, the clinical syndrome of ALF and its complications including multi-organ dysfunction and sepsis, are largely generated by the immune response to liver injury. Hepatic macrophages fulfil a diversity of roles in ALF, from pro-inflammatory to pro-resolution. Their inherent plasticity means the same macrophages may have a variety of functions depending on the local tissue environment at different stages of disease. A better understanding of the mechanisms that regulate macrophage plasticity during ALF will be an essential step towards realising the potential of immune-modulating therapies that re-orientate macrophages to promote the desirable functions of attenuating liver injury and promoting liver repair/regenerative responses. The key dynamics: temporal (early vs. late phase), regional (hepatic vs. systemic), and activation (pro-inflammatory vs. pro-resolution) are discussed and the potential for novel ALF therapies that modulate monocyte/macrophage function are described.
Department of Hepatology, St Mary's Campus, Imperial College London, London, UK.
Lucia A
LA
Possamai
Department of Hepatology, St Mary's Campus, Imperial College London, London, UK.
Mark R
MR
Thursz
Liver Intensive Care Unit, Institute of Liver Sciences, King's College London, London, UK.
Julia A
JA
Wendon
Department of Hepatology, St Mary's Campus, Imperial College London, London, UK; Liver Intensive Care Unit, Institute of Liver Sciences, King's College London, London, UK. Electronic address: c.antoniades@imperial.ac.uk.
Charalambos Gustav
CG
Antoniades
D000818:Animals; D016764:Cell Polarity; D060833:Cellular Microenvironment; D006801:Humans; D007113:Immunity, Innate; D017114:Liver Failure, Acute / Q000276:immunology* / Q000628:therapy; D008115:Liver Regeneration; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology
Acute liver failure; Biomarkers; Macrophage; Monocyte; Plasticity