Pro-Inflammatory and Anti-Inflammatory Cytokines Levels are Significantly Altered in Cerebrospinal Fluid of Unruptured Intracranial Aneurysm (UIA) Patients

Abstract

Introduction: Identifying all the relevant “players” in the formation and development of brain aneurysms may help understand the mechanisms responsible for the formation of an aneurysm, as well as in the search for non-invasive targets for aneurysm pharmacotherapy. Aim: The evaluation of the concentration of pro-inflammatory and anti-inflammatory cytokines in cerebrospinal fluid (CSF) and serum of patients with unruptured intracranial aneurysms (UIA) in comparison to individuals without vascular lesions in the brain. Methods: The concentration of 27 proteins in the CSF and serum of UIA patients (N = 40) and individuals without vascular lesions in the brain (N = 15) was evaluated using a multiplex ELISA kit (Bio-Plex Pro Human Cytokine 27-Plex Panel). Results: In the CSF 13 out of 27 proteins evaluated presented a concentration 1.36-fold or greater in UIA patients in comparison to the control group. Significantly higher were IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-7, IL-8, IL-12, IL-13, TNF-α, INF-γ, MCP-1, and VEGF. In the serum none of the proteins evaluated significantly differ between UIA patients and the control group. The correlation coefficient analysis showed that CSF IL-1β, IL-8, and TNF-α positively, while IL-13 negatively correlated with the size of aneurysms. CSF IL-6 and MCP-1 concentrations positively correlated with the number of aneurysms. Conclusion: In patients with UIA, pro-inflammatory and anti-inflammatory mechanisms are activated simultaneously, because the concentration of promoting and suppressing inflammatory response proteins was significantly higher in CSF of UIA patients compared to the control group. The preventive therapy of brain aneurysm development should be focused on IL-1β, IL-6, IL-8, MCP-1, and TNF-α, the concentration of which in CSF positively correlated with the size and number of aneurysms.