Glucocorticoid Resistance is Associated with Poor Functional Outcome After Stroke

Systemic inflammation is associated with poor outcome after stroke. Glucocorticoids (GCs) play a fundamental role in limiting inflammation. The aim of this study was to explore the associations between GC sensitivity, systemic inflammation, and outcome after ischemic stroke. The study population compised 246 ischemic stroke patients (median age: 69.0 years; 41.1% female). To assess GC sensitivity, we incubated venous blood samples that were obtained at day 3 after stroke with lipopolysaccharide (10 ng/mL) and dexamethasone (10(–6) mol/L). We defined the GC sensitivity index as the ratio of tumor necrosis factor α (TNFα) released after blood stimulation with lipopolysaccharide and dexamethasone to the amount of TNFα released after blood stimulation with lipopolysaccharide alone. A higher index indicates higher GC resistance. The patients with poor functional outcome had a higher GC sensitivity index than those with good outcome (median: 16.1% vs. 13.5%, P < 0.01). In a logistic regression analysis adjusted for age, stroke severity, pneumonia, leukocyte count, plasma interleukin-6, and TNFα release ex vivo, a higher GC sensitivity index was associated with a higher risk of poor outcome after stroke (OR 2.32, 95% CI 1.21–4.45, P = 0.01). In conclusion, GC resistance is associated with poor functional outcome after stroke.