OWE-015 Prostaglandin E2 mediates innate immune suppression in acute-on-chronic liver failure via the EP4 receptor

Maini, Alexander A.; Salles, Natalia Becares; Robinson, Nathan; Gilroy, Derek W.; O’Brien, Alastair

doi:10.1136/gutjnl-2018-bsgabstracts.208

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“…However, our separate single site study has demonstrated an identical phenotype of reduced TNF-a production in fresh whole blood from AD/ACLF patients stimulated with LPS, supporting this approach. 25 Furthermore, our laboratory assay was potentially able to differentiate between survivors and non-survivors, and mechanistic work has identified a potential novel mediator of CAID, suggesting that the approach has validity. The association of the inflammatory phenotype in those who died at 3 months with development of an elevated WCC and CRP strengthens the laboratory work and aids potential clinical approaches in the future.…”

Section: Discussionmentioning

confidence: 93%

Immune Regulatory Mediators in Plasma from Patients With Acute Decompensation Are Associated With 3-Month Mortality

Bécares

Härmälä

China

et al. 2020

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS: Infection is a common cause of death in patients with cirrhosis. We investigated the association between the innate immune response and death within 3 months of hospitalization. METHODS: Plasma samples were collected on days 1, 5, 10, and 15 from participants recruited into the albumin to prevent infection in chronic liver failure feasibility study. Patients with acute decompensated cirrhosis were given albumin infusions at 10 hospitals in the United Kingdom. Data were obtained from 45 survivors and 27 non-survivors. We incubated monocyte-derived macrophages from healthy individuals with patients' plasma samples and measured activation following lipopolysaccharide administration, determined by secretion of tumor necrosis factor and soluble mediators of inflammation. Each analysis included samples from 4 to 14 patients. RESULTS: Plasma samples from survivors vs non-survivors had different inflammatory profiles. Levels of prostaglandin E2 were high at times of patient hospitalization and decreased with albumin infusions. Increased levels of interleukin 4 (IL4) in plasma collected at day 5 of treatment were associated with survival at 3 months. Incubation of monocyte-derived macrophages with day 5 plasma from survivors, pre-incubated with a neutralizing antibody against IL4, caused a significant increase in tumor necrosis factor production to the level of non-survivor plasma. Although baseline characteristics were similar, non-survivors had higher white cell counts and levels of C-reactive protein and renal dysfunction. CONCLUSIONS: We identified profiles of inflammatory markers in plasma that are associated with 3-month mortality in patients with acute decompensated cirrhosis given albumin. Increases in prostaglandin E2 might promote inflammation within the first few days after hospitalization, and increased levels of plasma IL4 at day 5 are associated with increased survival. Clinicaltrialsregister.

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Section: Discussionmentioning

confidence: 93%