The inflammatory response is an unavoidable process and contributes to the destruction of cerebral tissue during the acute ischemic stroke (AIS) phase and has not been addressed fully to date. Insightful understanding of correlation of inflammatory mediators and stroke outcome may provide new biomarkers or therapeutic approaches for ischemic stroke. Here, we prospectively recruited 180 first-ever AIS patients within 72 hrs after stroke onset. We used the National Institutes of Health Stroke Scale (NIHSS) to quantify stroke severity and modified Rankin scale (mRS) to assess the 3-month outcome for AIS patients. Initially, we screened 35 cytokines, chemokines, and growth factors in sera from 75 AIS patients and control subjects. Cytokines that were of interest were further investigated in the 180 AIS patients and 14 heathy controls. We found that IL-1RA, IL-1β, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-13, IL-15, EGF, G-CSF, Flt-3L, GM-CSF and Fractalkine levels were significantly decreased in severe stroke patients. In particular, IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-15, G-CSF and GM-CSF were significantly reduced in AIS patients with poor outcome, compared to those with good prognosis. IL-6 was notably higher in the poor outcome group. Only IL-9 level decreased in the large infarct volume group. After adjusting for confounders, we found that IL-5 was an independent protective factor for prognosis in AIS patients with an adjusted OR of 0.042 (P = 0.007), whereas IL-6 was an independent risk predictor for AIS patients with an adjusted OR of 1.293 (P = 0.003). Our study suggests the levels of serum cytokines are related to stroke severity, short-term prognosis and cerebral infarct volume in AIS patients.

Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS.