Immune Regulatory Mediators in Plasma from Patients with Acute Decompensation are Associated With 3-month Mortality

Becares, Natalia, Härmälä, Suvi, China, Louise, Colas, Romain A., Maini, Alexander A., Bennet, Kate, Skene, Simon S., Shabir, Zainib, Dalli, Jesmond and O’Brien, Alastair (2019) Immune Regulatory Mediators in Plasma from Patients with Acute Decompensation are Associated With 3-month Mortality Clinical Gastroenterology and Hepatology.

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Abstract

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.eu: EudraCT 2014-002300-24

Item Type:	Article
Divisions :	Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :	Name Email ORCID Becares, Natalia Härmälä, Suvi China, Louise Colas, Romain A. Maini, Alexander A. Bennet, Kate Skene, Simon S. s.skene@surrey.ac.uk Shabir, Zainib Dalli, Jesmond O’Brien, Alastair
Date :	22 August 2019
Funders :	he Health Innovation Challenge fund (Wellcome Trust and Department of Health), The Rosetrees Trust, Biotechnology and Biological Sciences Research Council (BBSRC)
DOI :	10.1016/j.cgh.2019.08.036
Copyright Disclaimer :	© 2019 by the AGA Institute. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be
Uncontrolled Keywords :	TNF; MDM; Death; Immune response
Depositing User :	Diane Maxfield
Date Deposited :	26 Sep 2019 09:39
Last Modified :	26 Sep 2019 09:39
URI:	http://epubs.surrey.ac.uk/id/eprint/852805

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