Anti-inflammatory Effect Of Cilostazol On Silent Brain Infarction

Abstract

Introduction: Silent brain infarcts (SBI) are seen on brain computed topography or magnetic resonance imaging without any clinical symptoms suggestive of transient ischemic attack or stroke. SBI are associated with the risk of subsequent stroke and dementia. Various inflammatory markers have been reported to correlate with SBI. After the Cilostazol Stroke Prevention Study, many studies have focused on anti-inflammatory effect of cilostazol.Hypothesis: We investigated the anti-inflammatory effect of cilostazol in the patients with silent brain infarcts by measuring temporal profile of inflammatory markers.Methods: We prospectively and consecutively enrolled 26 patients with silent brain infarcts, who agreed signed informed consent, and then treated with cilostazol (200mg/day) for 3 months. Several inflammatory markers including macrophage migration inhibitory factor (MIF), stromal cell-derived factor-1 (SDF-1),vascular endothelial growth factor (VEGF), visfatin, and matrix metalloproteinase 9 (MMP-9) were repeatedly measured at baseline, 1 week, and 3 months.Results: Levels of MIF, visfatin, and MMP-9 were significantly decreased 3months after cilostazol treatmentwhen compared with baseline and 1week (p < 0.05). There is no significant difference in SDF-1 and VEGF.Conclusion: After cilostazol treatment for 3 months, MIF, visfatin, and MMP-9 among various inflammatory markers notably decreased. MIF has been reported as a pro-inflammatory marker by promoting cell death and facilitating the atherogenesis process. Visfatin stimulates the release of cytokines and is induced by inflammatory stimuli in cells involved in innate immunity, such as neutrophils, monocytes, macrophages, and epithelial cells. MMP-9 has been shown to contribute to blood-brain barrier disruption, infarct formation and hemorrhagic transformation. Therefore, these factors play important roles in pathogenesis or consequence after ischemic stroke. Based on our findings, we cautiously suggest that cilostazol has anti-inflammatory effect affecting inflammatory markers such as MIF, visfatin and MMP-9 and further investigation about relationship between these markers and clinical significance is needed.