Monocytes Are Major Players in the Prognosis and Risk of Infection After Acute Stroke

被引:207
作者
Urra, Xabier [2 ]
Cervera, Alvaro [2 ]
Obach, Victor [2 ]
Climent, Nuria [3 ,4 ]
Planas, Anna M. [3 ,5 ]
Chamorro, Angel [1 ,2 ,3 ]
机构
[1] Univ Barcelona, Fac Med, Inst Neurosci, E-08036 Barcelona, Spain
[2] Hosp Clin Barcelona, Funct Unit Cerebrovasc Dis, Barcelona, Spain
[3] IDIBAPS, Barcelona, Spain
[4] Hosp Clin Barcelona, Serv Immunol, Barcelona, Spain
[5] CSIC, IIBB, Barcelona, Spain
关键词
acute stroke; flow cytometry; immunology; monocytes; stroke-associated infection; ACUTE ISCHEMIC-STROKE; TOLL-LIKE RECEPTOR-2; INDUCED IMMUNODEPRESSION; INFLAMMATORY RESPONSE; IMMUNE-RESPONSES; BRAIN-DAMAGE; ACTIVATION; EXPRESSION; TOLL-LIKE-RECEPTOR-4; HYPERCORTISOLISM;
D O I
10.1161/STROKEAHA.108.532085
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
Background and Purpose-Monocytes participate in adaptive and innate immune responses. Monocyte numbers increase in patients with stroke associated infection (SAI) or severe stroke. Whether changes in monocytes are related to specific effects, or simply mark brain damage, remains unsettled. Methods-We used flow cytometry in 45 consecutive strokes and 12 healthy controls to assess the time course of monocytes, their phenotype, and the production of cytokines after stimulation. Cortisol, TNF-alpha, IFN-gamma, and IL-10 were measured in serum and metanephrine in plasma. The effects of Immoral and cellular parameters on the risk of SAI and poor outcome were tested in multivariate analyses adjusted for confounders (NIHSS score, age, and tube feeding). Results-Surface expression of human leukocyte antigen-DR, Toll-like receptor-2, and production of TNF-a in monocytes were independently associated with stroke. Distinct immune mechanisms were related with functional outcome and the risk of SAI; the signature of SAI included an increase of cortisol, metanephrine, and IL-10 in serum, and reduced production of TNF-a in monocytes; poor outcome was associated with increased expression of Toll-like receptor-4 in monocytes (OR, 9.61; 95% CI, 1.27-72.47). SAI did not predict poor outcome (OR, 5.63; 95% CI, 0.45-70.42; P=0.18). Conclusions-In human stroke, poor outcome is associated to innate responses mediated by Toll-like receptor-4 in monocytes. SAI may result from the immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL-10, and deactivated monocytes. Early treated SAI does not contribute significantly to additional brain damage. These findings encourage the exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in acute stroke. (Stroke. 2009;40:1262-1268.)
引用
收藏
页码:1262 / 1268
页数:7
相关论文
共 43 条
[1]
SURFACE EXPRESSION OF ALPHA-4 INTEGRIN BY CD4 T-CELLS IS REQUIRED FOR THEIR ENTRY INTO BRAIN PARENCHYMA [J].
BARON, JL ;
MADRI, JA ;
RUDDLE, NH ;
HASHIM, G ;
JANEWAY, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (01) :57-68
[2]
Inflammatory mediators and stroke: New opportunities for novel therapeutics [J].
Barone, FC ;
Feuerstein, GZ .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1999, 19 (08) :819-834
[3]
Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses [J].
Beg, AA .
TRENDS IN IMMUNOLOGY, 2002, 23 (11) :509-512
[4]
Toll-like receptor 4 is involved in subacute stress-induced neuroinflammation and in the worsening of experimental stroke [J].
Caso, Javier R. ;
Pradillo, Jesus M. ;
Hurtado, Olivia ;
Leza, Juan C. ;
Moro, Maria A. ;
Lizasoain, Ignacio .
STROKE, 2008, 39 (04) :1314-1320
[5]
Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke [J].
Caso, Javier R. ;
Pradillo, Jesus M. ;
Hurtado, Olivia ;
Lorenzo, Pedro ;
Moro, Maria A. ;
Lizasoain, Ignacio .
CIRCULATION, 2007, 115 (12) :1599-1608
[6]
Monocytes/macrophages and sepsis [J].
Cavaillon, JM ;
Adib-Conquy, M .
CRITICAL CARE MEDICINE, 2005, 33 (12) :S506-S509
[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]
The harms and benefits of inflammatory and immune responses in vascular disease [J].
Chamorro, A ;
Hallenbeck, J .
STROKE, 2006, 37 (02) :291-293
[9]
The early systemic prophylaxis of infection after stroke study - A randomized clinical trial [J].
Chamorro, A ;
Horcajada, JP ;
Obach, V ;
Vargas, M ;
Revilla, M ;
Torres, F ;
Cervera, A ;
Planas, AM ;
Mensa, J .
STROKE, 2005, 36 (07) :1495-1500
[10]
Infection after acute ischemic stroke - A manifestation of brain-induced immunodepression [J].
Chamorro, Angel ;
Urra, Xabier ;
Planas, Anna M. .
STROKE, 2007, 38 (03) :1097-1103