Cerebral blood flow and oxidative metabolism during human endotoxemia

Abstract

The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α), has been suggested to mediate septic encephalopathy through an effect on cerebral blood flow (CBF) and metabolism. The effect of an intravenous bolus of endotoxin on global CBF, metabolism, and net flux of cytokines and catecholamines was investigated in eight healthy young volunteers. Cerebral blood flow was measured by the Kety-Schmidt technique at baseline (during normocapnia and voluntary hyperventilation for calculation of subject-specific cerebrovascular CO2 reactivity), and 90 minutes after an intravenous bolus of a reference Escherichia coli endotoxin. Arterial TNF-α peaked at 90 minutes, coinciding with a peak in subjective symptoms. At this time, CBF and Paco2 were significantly reduced compared to baseline; the CBF decrease was readily explained by hypocapnia. The cerebral metabolic rate of oxygen remained unchanged, and the net cerebral flux of TNF-α, interleukin (IL)-1β, and IL-6 did not differ significantly from zero. Thus, high circulating levels of TNF-α during human endotoxemia do not induce a direct reduction in cerebral oxidative metabolism.