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. Aim To determine the relationship of brain cytokine production with severity of intracranial hypertension in ALF patients. Method 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-1 beta) 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-1 beta 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. Conclusion 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.