Plasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome

• Toll-like receptor 4 plays a role in ischemic brain damage.
• Endotoxin (LPS) is an agonist of Toll-like receptor 4.
• Plasma LPS activity is higher in ischemic stroke patients than in controls.
• Plasma LPS activity rises during ischemic stroke.
• Higher plasma LPS activity is associated with worse short-term outcome.

BackgroundActivation of Toll-like receptor 4 (TLR4) contributes to brain injury and poor outcome after cerebral ischemia. The expression of this receptor on monocytes is increased in patients with acute ischemic stroke. Endotoxin is an endogenous ligand for TLR4. The aim of our study was to determine if plasma endotoxin activity is increased in stroke patients and correlates with functional outcome.MethodsWe included 88 patients with ischemic stroke (median age: 71, 56.8% men) and 59 age-matched controls. Plasma endotoxin activity and level of proteins regulating endotoxin interaction with TLR4 (LPS binding protein – LBP and sCD14) were measured in blood samples taken at day 1 (within 24 h after stroke symptoms onset), 3 and 6. Short-term functional outcome was assessed at day 14 using modified Rankin Scale. Unfavourable outcome was defined as modified Rankin Scale score > 2.ResultsCompared to controls, stroke patients had higher plasma endotoxin activity on day 1 (median: 0.39 vs 0.32 EU/mL, P = 0.03) as well as higher LBP (median: 18.7 vs 11.5 μg/mL, P < 0.01) and sCD14 level (median: 1330 vs 1070 ng/mL, P < 0.01). Plasma LPS activity and levels of LBP and sCD14 significantly rose during stroke. Higher LPS activity measured on day 6 was associated with unfavourable outcome (OR: 3.94, 95%CI: 1.03–15.02, P = 0.04, adjusted for age and stroke severity).ConclusionsPlasma endotoxin activity rises during ischemic stroke and is associated with worse short-term outcome.

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