title: Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension.
abstract: BACKGROUND
  In acute liver failure (ALF), it is unclear whether the systemic inflammatory response associated with intracranial hypertension is related to brain cytokine production.
  
  
  OBJECTIVE
  To determine the relationship of brain cytokine production with severity of intracranial hypertension in ALF patients.
  
  
  METHODS
  We studied 16 patients with ALF. All patients were mechanically ventilated and cerebral blood flow measured using the Kety-Schmidt technique and intracranial pressure (ICP) measured with a Camino subdural catheter. We sampled blood from an artery and a reverse jugular catheter to measure proinflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) and ammonia. Additionally, in 3 patients, serial samples were obtained over a 72 h period.
  
  
  RESULTS
  In ALF patients a good correlation between arterial pro-inflammatory cytokines and ICP (r (2) = 0.34, 0.50 and 0.52; for IL-6, IL-1beta and TNF-alpha respectively) was observed. There was a positive cerebral cytokine 'flux' (production), in ALF patients with uncontrolled ICP. Plasma ammonia between groups was not statistically significant. In the ALF patients studied longitudinally, brain proinflammatory cytokine production was associated with uncontrolled ICP.
  
  
  CONCLUSIONS
  Our results provide novel data supporting brain production of cytokines in patients with uncontrolled intracranial hypertension indicating activation of the inflammatory cascade in the brain. Also, the appearance of these cytokines in the jugular bulb catheter may indicate a compromised blood brain barrier at this late stage.
authors: Liver Failure Group, The Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London, UK.
authors: Gavin
authors: G
authors: Wright
authors: Debbie
authors: D
authors: Shawcross
authors: Steven W M
authors: SW
authors: Olde Damink
authors: Rajiv
authors: R
authors: Jalan
mesh_terms: D000328:Adult; D000641:Ammonia / Q000378:metabolism; D001921:Brain / Q000276:immunology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis*; D006501:Hepatic Encephalopathy / Q000209:etiology; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D019586:Intracranial Hypertension / Q000209:etiology*; D017114:Liver Failure, Acute / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000641:Ammonia