Objectives:To assess the relationship between blood biomarkers of inflammation and lesion growth within the penumbra in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT).Methods:HIBISCUS-STROKE cohort enrolled patients admitted in the Lyon Stroke Center for an anterior circulation AIS treated with MT following MRI. Lesion growth within the penumbra was assessed on day-6 MRI using a voxel-based nonlinear coregistration method and dichotomized into low and high according to the median. C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1), soluble tumor necrosis factor receptor I (sTNF-RI), soluble form suppression of tumorigenicity 2 (sST2), soluble P-selectin (sP-selectin), vascular cellular adhesion molecule-1 (VCAM-1) and matrix metalloproteinase-9 (MMP-9) were measured in sera at 4 timepoints within the first 48 hours. Reperfusion was considered as successful if Thrombolysis in Cerebral Infarction (TICI) score was 2b/2c/3. A multiple logistic regression model was performed to detect any association between area under the curve (AUC) of these biomarkers within the first 48 hours and a high lesion growth within the penumbra.Results:90 patients were included. Median lesion growth within the penumbra was 2.3 [0.7-6.2] mL. On multivariable analysis, a high sST2 AUC (odds ratio (OR) 3.77, 95% confidence interval (CI) 1.36-10.46) as well as a high baseline DWI volume (OR 3.65, 95% CI 1.32-10.12) and lack of successful reperfusion (OR 0.19, 95% CI 0.04-0.92) were associated with a high lesion growth within the penumbra. When restricting analyses to patients with successful reperfusion (n=76), a high sST2 AUC (OR 5.03, 95% CI 1.64-15.40), a high baseline DWI volume (OR 3.74, 95% CI 1.22-11.53) and a high penumbra volume (OR 3.25, 95% CI 1.10-9.57) remained associated with a high lesion growth within the penumbra.Conclusions: sST2 levels within the first 48 hours are associated with a high lesion growth within the penumbra.