Article
Immunophenotyping of intrathecal inflammatory response in aneurysmatic subarachnoid haemorrhage reveals distinct monocytic activation and chemokine patterns
Immunphänotypisierung der intrathekalen Inflammation bei aneurysmatischer subarachnoidaler Blutung zeigt distinkte Monozytenaktivierung und Chemokine-Produktion
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Published: | May 8, 2019 |
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Objective: The pathophysiology of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is still incompletely understood. Intrathecal inflammatory immune activation is suspected to play a major role for the induction of vasospasm and DCI. The aim of this study is to identify immune cell subsets and inflammatory mediators involved in the pathogenesis of DCI.
Methods: We prospectively collected blood and cerebrospinal fluid (CSF) from 25 patients with aneurysmal subarachnoid hemorrhage at an early and a late time points. Fifteen immune cell subsets were analyzed using a multicolor antibody panel and flow cytometry. In addition, 26 chemokines and T helper cell cytokines were assessed using a bead-based immunofluorescence assay. Statistical testing and correlative analysis were performed for Hunt & Hess grading, overall outcome and prevalence of DCI.
Results: Our results demonstrate an intrathecal immune activation with increased prevalence of conventional CD4 T cells (CD4+ CD25+), as well as expression of the CD163 scavenger receptor on monocytes. The inflammatory response was also reflected in increased IFNy production (p<0.05), CD11c+ infiltration and prevalence of plasmacytoid dendritic cells (pDC). Initially present CD14dim activated monocytes converted to classical CD14- CD16+ monocytes throughout the disease course. The intrathecal chemokine response was represented by IP-10, MIG, I-TAC and GROa (p=0.05–0.0001), chemoattractants contributing to the recruitment of additional immune cells to the site of inflammation. Statistical analysis shows strong correlation of distinct patterns to the prevalence of DCI and outcome.
Conclusion: We demonstrate that monocytes and T cells are activated intrathecally during aSAH and mediate a local inflammatory response which is presumably driven by interferons and the subsequent chemokine cascade. Our data shows that the distinct pattern of immune activation correlates to the prevalence of DCI, indicating a pathophysiological connection to the incidence of vasospasm.