PGE2 and immune suppression in decompensated cirrhosis

• Research type

  Research Study

• Full title

  An investigation of suppression of cirrhosis-mediated immune suppression by prostaglandin receptor antagonism.

• IRAS ID

  170839

• Contact name

  Alastair O'Brien

• Contact email

  a.o'brien@ucl.ac.uk

• Sponsor organisation

  University College London

• Duration of Study in the UK

  3 years, 6 months, 28 days

• Research summary

  Unlike other common causes of death in the UK, which are static or declining, death from liver disease continues to rise and it is now the 5th commonest cause of death. Infection is the major cause of death in patients with advanced liver disease and these patients have an increased susceptibility to bacterial infection. One of the major underlying causes of this susceptibility is immune suppression.
  In view of their poor outcome from infection liver patients are currently treated aggressively with broad spectrum antibiotics even when there is little evidence of active infection. However this approach has led to little improvement in mortality rates over the last 20 years. Antibiotics may also cause harmful side-effects (e.g. diarrhoea) and overuse has led to antibiotic resistant bacteria which makes these crucial drugs much less effective and will be one of medicine's greatest challenges over the next decade.
  We have recently demonstrated that an increased blood level of a lipid hormone, Prostaglandin E2, is an important mediator of immune suppression in patients with advanced liver disease. We wish to pinpoint the sources of PGE2 as well as the receptor/s through which it mediates its immune suppressive effects and use this information to guide drug development that we hope will lead to improved treatment of infection in these patients.
  We will use standard laboratory techniques to investigate PGE2 signalling pathways on samples obtained from both experimental models and humans including liver tissue, bronchoalveolar lavage fluid, urine, blood, stool and ascitic fluid. We shall use this information to determine which represents the optimum site of inhibition for further drug development using a novel skin blister multiple-chamber model that permits dynamic study of infection in patients with liver disease.

• REC name

  London - South East Research Ethics Committee

• REC reference

  15/LO/0800

• Date of REC Opinion

  16 Jun 2015

• REC opinion

  Further Information Favourable Opinion