Brain cytokine flux in acute liver failure and its relationship with intracranial hypertension.
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.
Wright
Gavin
G
Liver Failure Group, The Institute of Hepatology, Division of Medicine, University College London, 69-75 Chenies Mews, London, UK.
Shawcross
Debbie
D
Olde Damink
Steven W M
SW
Jalan
Rajiv
R
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
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000641:Ammonia