HARMS AND BENEFITS OF LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH ACUTE STROKE

被引:209
作者
Urra, X. [1 ]
Cerveraa, A. [1 ]
Villamor, N. [2 ]
Planas, A. M. [3 ,4 ]
Chamorro, A. [1 ,3 ,5 ]
机构
[1] Hosp Clin Barcelona, Funct Unit Cerebrovasc Dis, Barcelona, Spain
[2] Hosp Clin Barcelona, Hematopathol Unit, Barcelona, Spain
[3] Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain
[4] Consejo Superior Invest Cient, Inst Invest Biomed Barcelona, Barcelona, Spain
[5] Univ Barcelona, Fac Med, Barcelona 7, Spain
关键词
stroke; lymphocytes; stroke-associated infection; outcome; ACUTE ISCHEMIC-STROKE; POTENTIAL THERAPEUTIC TARGET; INFLAMMATION-MEDIATED DAMAGE; CEREBRAL-ARTERY OCCLUSION; VASCULAR-DISEASE; CEREBROSPINAL-FLUID; IMMUNE-SYSTEM; INFARCT SIZE; BRAIN-INJURY; HEAD-INJURY;
D O I
10.1016/j.neuroscience.2008.06.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Lymphocytes are major players in the development of innate and adaptive immune responses but their behavior in patients with acute stroke has received little attention. Experimental procedures: Using flow cytometry we identified total lymphocytes, T cells, helper T (Th) cells, cytotoxic T lymphocytes (CTL), natural killer (NK) cells, B cells, and regulatory T (Treg) cells in 46 consecutive patients with acute stroke within a median of 180 min of clinical onset, and at days 2, 7, and 90. Daily neurological score (National Institutes of Health Stroke Scale), diffusion-weighted imaging on brain magnetic resonance imaging, functional impairment, and stroke-associated infection (SAI) at day 7 were assessed. Apoptosis in lymphocyte subsets, tumor necrosis factor (TNF) -alpha/interieukin (IL) -4 production in stimulated Th and CTL, cluster of differentiation 86 (CD86) (B7-2) expression in B cells, cortisol and metanephrine in serum were measured. Multivariate analyses were used to evaluate SAI, and stroke outcome. Results: Increased apoptosis and a fall of T, Th, CTL, B, and Treg cells were observed after stroke. Severer stroke on admission and SAI disclosed a greater decline of T, Th, and CTL cells. Increased cortisol and metanephrine was associated with severe stroke and SAI, and inversely correlated with T, and CTL. T cells, and CTL were correlated with infarct growth. Stroke but not SAI resulted in lower TNF-alpha production in Th cells. SAI showed the greatest fall of lymphocytes, T, Th, and CTL, but not B cells, or Treg. Poor outcome was associated with reduced levels of B cells, and increased expression of CD86 in B cells, but not with SAL Conclusion: Lymphopenia and increased apoptosis of T, Th, CTL, Treg and B cells are early signatures after human stroke. A decreased cellular response after stroke is a marker of ongoing brain damage, the stress response, and a higher risk of infection. A lower humoral response is predictor of poorer long-term outcome. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:1174 / 1183
页数:10
相关论文
共 58 条
[1]   Adoptive transfer of myelin basic protein-tolerized splenocytes to naive animals reduces infarct size - A role for lymphocytes in ischemic brain injury? [J].
Becker, K ;
Kindrick, D ;
McCarron, R ;
Hallenbeck, J ;
Winn, R .
STROKE, 2003, 34 (07) :1809-1815
[2]   Antibody to the α4 integrin decreases infarct size in transient focal cerebral ischemia in rats [J].
Becker, K ;
Kindrick, D ;
Relton, J ;
Harlan, J ;
Winn, R .
STROKE, 2001, 32 (01) :206-211
[3]   IMMUNOREGULATORY FEEDBACK BETWEEN INTERLEUKIN-1 AND GLUCOCORTICOID HORMONES [J].
BESEDOVSKY, H ;
DELREY, A ;
SORKIN, E ;
DINARELLO, CA .
SCIENCE, 1986, 233 (4764) :652-654
[4]   THE IMMUNE-RESPONSE EVOKES CHANGES IN BRAIN NORADRENERGIC NEURONS [J].
BESEDOVSKY, H ;
DELREY, A ;
SORKIN, E ;
DAPRADA, M ;
BURRI, R ;
HONEGGER, C .
SCIENCE, 1983, 221 (4610) :564-566
[5]   ROLE OF THE LYMPHATIC-SYSTEM IN DRAINAGE OF CEREBROSPINAL-FLUID AND AQUEOUS-HUMOR [J].
BRADBURY, MWB ;
COLE, DF .
JOURNAL OF PHYSIOLOGY-LONDON, 1980, 299 (FEB) :353-365
[6]   Inflammation-mediated damage in progressing lacunar infarctions -: A potential therapeutic target [J].
Castellanos, M ;
Castillo, J ;
García, MM ;
Leira, R ;
Serena, J ;
Chamorro, A ;
Dávalos, A .
STROKE, 2002, 33 (04) :982-987
[7]   Interleukin 10, monocytes and increased risk of early infection in ischaemic stroke [J].
Chamorro, A. ;
Amaro, S. ;
Vargas, M. ;
Obach, V. ;
Cervera, A. ;
Torres, F. ;
Planas, A. M. .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2006, 77 (11) :1279-1281
[8]  
Chamorro A, 2004, E SCHERING RES FDN W, V47, P185
[9]   Role of inflammation in stroke and atherothrombosis [J].
Chamorro, A .
CEREBROVASCULAR DISEASES, 2004, 17 :1-5
[10]   EARLY PREDICTION OF STROKE SEVERITY - ROLE OF THE ERYTHROCYTE SEDIMENTATION-RATE [J].
CHAMORRO, A ;
VILA, N ;
ASCASO, C ;
SAIZ, A ;
MONTALVO, J ;
ALONSO, P ;
TOLOSA, E .
STROKE, 1995, 26 (04) :573-576