Modulation of monocyte/macrophage function: A therapeutic strategy in the treatment of acute liver failure

TY - JOUR

T1 - Modulation of monocyte/macrophage function

T2 - A therapeutic strategy in the treatment of acute liver failure

AU - Possamai, Lucia A.

AU - Thursz, Mark R.

AU - Wendon, Julia A.

AU - Antoniades, Charalambos Gustav

PY - 2014/8

Y1 - 2014/8

N2 - 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 ALP 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.

AB - 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 ALP 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.

KW - Acute liver failure

KW - Macrophage

KW - Monocyte

KW - Plasticity

KW - Biomarkers

KW - INFLAMMATORY RESPONSE SYNDROME

KW - ACETAMINOPHEN-INDUCED HEPATOTOXICITY

KW - GROUP BOX 1

KW - ALBUMIN DIALYSIS

KW - INFILTRATING MACROPHAGES

KW - HEPATIC-ENCEPHALOPATHY

KW - ALPHA-FETOPROTEIN

KW - SOLUBLE CD163

KW - KUPFFER CELLS

KW - ORGAN FAILURE

U2 - 10.1016/j.jhep.2014.03.031

DO - 10.1016/j.jhep.2014.03.031

M3 - Article

SN - 0168-8278

VL - 61

SP - 439

EP - 445

JO - Journal of Hepatology

JF - Journal of Hepatology

IS - 2

ER -