Dataset Information

Monocyte phenotype indicates a poor prognosis in paracetamol (acetaminophen) induced acute liver failure but not in non-ae hepatitis: a prospective observational cohort study

ABSTRACT: Acute liver failure (ALF) is a rare but serious medical syndrome associated with significant morbidity and mortality. Paracetamol (acetaminophen) hepatotoxicity is the most common cause in many parts of the world. Recent studies have implicated the patient’s immune response to the tissue injury is important in dictating clinical outcome, especially monocyte/macrophage cells of the innate immune system. Patients with the worst clinical outcomes after a paracetamol overdose (POD) (death/emergency liver transplant) had a significant and prolonged monocytopenia characterised by reduced classical and expanded intermediate monocyte subset population. This same change was seen in the mouse monocytes but did not occur in patients with non-AE hepatitis. In POD patients, this was associated with reduced circulating lymphocytes and NK cells, peripheral cytokine patterns suggestive of a “cytokine storm” and increased circulating concentrations of cytokines associated with monocyte egress from the bone marrow. Monocyte gene expression did not differentiate patient outcome. Severe paracetamol induced hepatotoxicity is associated with profound changes in the cells of the peripheral blood compartment that are related to patient outcome especially the circulating monocytes. This is not seen in patients with non-AE hepatitis. Such changes may allow earlier definition of prognosis or highlight potential for therapeutic intervention utilising monocytes to improve outcomes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE80751 | GEO | 2019/04/27

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Monocytes and macrophages are implicated in inflammation and atherosclerosis, whereas monocytes are involved in psoriasis lesion formation. We previously reported a psoriatic inflammation-associated significant decrease in the membrane protein caveolin-1 (CAV-1) in psoriasis patient monocytes. However, the phenotype of circulating monocytes and their macrophage differentiation in psoriasis patients remain unclear. Objective: We sought to clarify circulating monocyte and monocyte-derived macrophage (MDM) phenotypes in psoriasis patients with and without comorbidities. Method: Thirty-one patients with psoriasis vulgaris and 28 control subjects were included. Surface macrophage markers and inflammatory status were examined in circulating monocytes and MDMs from both groups. Expression of CD36, which mediates macrophage uptake of oxidized low-density lipoprotein (oxLDL), was evaluated in these cells. CAV-1-silenced monocytes were differentiated into macrophages to investigate the effects of CAV-1 downregulation on psoriatic inflammation and atherosclerosis. Results: Macrophage surface markers were detectable in circulating monocytes. A significant M1 shift was detected in monocytes and MDMs in psoriasis patients, including those without cardiovascular disease risk factors, as compared to controls. MDMs of psoriasis patients had more CD36-expressing cells, which are associated with atherosclerosis risk. Additionally, CAV-1-silencing in monocytes increased the likelihood of M1-biased macrophage differentiation and increased pro-inflammatory cytokine production. Conclusions: Monocytes from psoriasis patients were more likely to differentiate into M1-dominant macrophages, correlating with inflammatory status and CAV-1 expression. These aberrant inflammatory monocytes not only contribute to psoriatic inflammation by producing psoriatic cytokines, but also have a phenotype that could increase atherosclerosis risk by uptake of oxLDL and formation of foam cells.

Dataset Information

Monocyte phenotype indicates a poor prognosis in paracetamol (acetaminophen) induced acute liver failure but not in non-ae hepatitis: a prospective observational cohort study

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets