RESUMO
Chemokines are vital in post-cerebral ischemia inflammatory reactions. We investigate the possible relationship between plasma chemokines and short-term and long-term outcomes after stroke. This study included 235 patients (median age, 72 years; 49.8% female) suffering from ischemic stroke, or transient ischemic attack admitted to the hospital within 24 h of onset. We evaluated chemokines CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in plasma samples collected upon admission. Further, we assessed functional outcomes at 3- and 12-months, all-cause fatality over 5 years, and episodes of delirium within the first 7 days of admission. Multivariate analysis revealed an association between higher CXCL10 levels and an increased risk of poor functional outcomes at 3 months (OR: 3.02, 95%CI: 1.22-7.46, p = 0.016) and 12 months (OR: 2.32, 95%CI: 1.03-5.26, p = 0.043), as well as an increased death risk (HR: 1.79, 95%CI: 1.04-3.07, p = 0.036). High CXCL8 levels independently predicted poor functional outcomes at 12 months (OR: 2.69, 95%CI: 1.39-6.31, p = 0.005) and a higher 5-year case fatality rate (HR: 1.90, 95%CI: 1.23-2.93, p = 0.004). Elevated CXCL9 levels also predicted unfavourable functional outcomes at 12 months (OR: 2.45, 95%CI: 1.07-5.61, p = 0.034). In univariate analysis, increased levels of CXCL8, CXCL9, and CXCL10 showed an association with delirium, although this link was not evident in the multivariate analysis. Plasma CXCL8 and CXCL10 show potential as prognostic biomarkers for stroke outcomes and as therapeutic targets suitable for reverse translation.
RESUMO
OBJECTIVE: Fatigue is a common, debilitating syndrome after stroke. Peripheral inflammation plays a role in the pathogenesis of fatigue of different origin, but its contribution to post-stroke fatigue (PSF) remains unclear. We aimed to determine if there is any association between ex vivo synthesized and circulating cytokines, and risk of PSF. METHODS: We included 174 patients with ischemic stroke. We stimulated in vitro blood taken on day 3 after stroke with endotoxin. We measured ex vivo released (TNFα, IP-10, IL-1ß, IL-6, IL-8, IL-10, IL-12p70) and plasma (TNFα, IL-6, sIL-6R, IL-1Ra) cytokines. We assessed fatigue at month 3 using Fatigue Severity Scale (FSS). We used logistic regression to assess the relationship between cytokines and fatigue scores. RESULTS: Compared with patients with lower fatigue at month 3 (FSS < 36), patients with higher fatigue (FSS ≥ 36) had lower endotoxin-stimulated TNFα release after 24 h (median: 429 vs 581 pg/mL, P = 0.05). Plasma TNFα tended to be higher in patients who developed fatigue (median: 0.8 vs 0.6 pg/mL, P = 0.06). Other cytokines did not differ between groups. After adjusting for pre-stroke fatigue and depressive symptoms, TNFα release <559.7 pg/mL after 24 h was associated with an increased risk of PSF (OR: 2.61, 95%CI: 1.22-5.57, P = 0.01). Plasma TNFα >0.76 pg/mL was associated with higher risk of PSF in univariable (OR: 2.41, 95%CI: 1.13-5.15, P = 0.02), but not multivariable analysis (OR: 2.41, 95%CI: 0.96-6.00, P = 0.06). CONCLUSION: Reduced ex vivo TNFα synthesis upon whole blood stimulation with endotoxin in the acute phase of stroke predicted PSF.
