Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2

Alastair J. O'Brien, James N. Fullerton, Karen A. Massey, Grace Auld, Gavin Sewell, Sarah James, Justine Newson, Effie Karra, Alison Winstanley, William Alazawi, Rita Garcia-Martinez, Joan Cordoba, Anna Nicolaou, Derek W. Gilroy

    Research output: Contribution to journalArticlepeer-review


    Liver disease is one of the leading causes of death worldwide. Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system; however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin E2 (PGE2) drives cirrhosis-associated immunosuppression. We observed elevated circulating concentrations (more than seven times as high as in healthy volunteers) of PGE2 in patients with acute decompensation of cirrhosis. Plasma from these and patients with end-stage liver disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and bacterial killing in vitro in a PGE2-dependent manner via the prostanoid type E receptor-2 (EP2), effects not seen with plasma from patients with stable cirrhosis (Child-Pugh score grade A). Albumin, which reduces PGE2 bioavailability, was decreased in the serum of patients with acute decompensation or ESLD (
    Original languageEnglish
    Pages (from-to)518–523
    JournalNature Medicine
    Publication statusPublished - 13 Apr 2014


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