57 Secretory Leukocyte Protease Inhibitor (Slpi) Is a Pivotal Mediator of Anti-Inflammatory Responses in Acute Liver Failure

Chemokine (C‐C motif) receptor 2–positive monocytes aggravate the early phase of acetaminophen‐induced acute liver injury

“…In accord with these experimental data from mouse models, we could clearly demonstrate the abundant presence of CCR2 1 and S100A9 1 proinflammatory MoMFs in the portal tracts in livers of patients with AALF, whereas CD163 1 anti-inflammatory macrophages (33) as well as CD68 1 resident macrophages are not restricted to the portal tracts. The fact that these findings have been obtained from AALF patients that required liver transplantation corroborates the suggested contribution of MoMF-related proinflammatory responses to detrimental liver injury.…”

“…In order to further characterize the infiltrating CCR2 1 MoMFs, we stained for S100A9 as a proinflammatory marker (32) and the secretory leukocyte protease inhibitor (CD163) as an anti-inflammatory macrophage marker in AALF. (33) CCR2 1 cells mainly clustered around the portal tract, indicating that these cells have recently infiltrated the liver, whereas CD68 1 macrophages are equally distributed between the portal tract and the remaining parenchyma ( Fig. 7C).…”

Inflammasome activation and function in liver disease

“…9,118,121 Undoubtedly, innate immune signalling and the inflammasome are activated in paracetamol-mediated hepatotoxicity. 45,130 Consequently, one can conclude that DAMPs and the inflammasome are critical determinants of paracetamol-mediated liver inflammation, but have only a limited role in the extent of hepatocyte death triggered early in injury progression by paracetamol metabolites. [121][122][123] However, whether the inflammasome modulates liver regeneration in the recovery phase of paracetamol-mediated injury, which might be critical for the long-term outcome, is unknown.…”