气候变化领域集成服务门户(CCPortal): Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone

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DOI	10.1073/pnas.2024852118
	Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone
	Whitworth L.J.; Troll R.; Pagán A.J.; Roca F.J.; Edelstein P.H.; Troll M.; Tobin D.M.; Phu N.H.; Bang N.D.; Thwaites G.E.; Thuong Thuong N.T.; Sewell R.F.; Ramakrishnan L.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Adjunctive treatment with antiinflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates with a C/T variant in Leukotriene A4 Hydrolase (LTA4H), which regulates expression of the proinflammatory mediator leukotriene B4 (LTB4). TT homozygotes, with increased expression of LTA4H, have the highest survival when treated with dexamethasone and the lowest survival without. While the T allele is present in only a minority of the world’s population, corticosteroids confer modest survival benefit worldwide. Using Bayesian methods, we examined how pretreatment levels of cerebrospinal fluid proinflammatory cytokines affect survival in dexamethasone-treated tuberculous meningitis. LTA4H TT homozygosity was associated with global cytokine increases, including tumor necrosis factor. Association between higher cytokine levels and survival extended to non-TT patients, suggesting that other genetic variants may also induce dexamethasone-responsive pathological inflammation. These findings warrant studies that tailor dexamethasone therapy to pretreatment cerebrospinal fluid cytokine concentrations, while searching for additional genetic loci shaping the inflammatory milieu. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Bayesian analysis; Corticosteroids; Cytokines; Inflammation; Tuberculous meningitis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180329
作者单位	Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, CB2 0QH, United Kingdom; Medical Research Council Laboratory of Molecular Biology, Cambridge, CB2 0QH, United Kingdom; Trinity College, Cambridge, CB2 1TQ, United Kingdom; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, United States; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, United States; Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam; Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, United Kingdom
推荐引用方式 GB/T 7714	Whitworth L.J.,Troll R.,Pagán A.J.,et al. Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone[J],2021,118(10).
APA	Whitworth L.J..,Troll R..,Pagán A.J..,Roca F.J..,Edelstein P.H..,...&Ramakrishnan L..(2021).Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Whitworth L.J.,et al."Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).