title: Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage.
abstract: Intracerebral hemorrhage (ICH) leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage (ICH). The results showed that fingolimod decreased the numbers of circulating CD4(+) T, CD8(+) T, CD19(+) B, NK, and NKT cells and they recovered quickly after the drug was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chang
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.|Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, China.
authors.forename: Yuanchu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.|Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, College of Life Sciences, Shaanxi Normal University, Xi'an, 710062, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Wood
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.|Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, 85013, USA.
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. yfu@tijmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. yaping.yan@tijmu.edu.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yan
mesh_terms: D002199:Capillary Permeability / Q000187:drug effects*; D002469:Cell Separation; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D008214:Lymphocytes / Q000187:drug effects; D016037:Single-Blind Method
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D000068876:Fingolimod Hydrochloride
keywords: fingolimod; inflammatory mediator; intracerebral hemorrhage; vascular permeability