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

Urra, Xabier; Cervera, Álvaro; Obach, Vı́ctor; Climent, Núria; Planas, Anna M.; Chamorro, Ángel

doi:10.1161/strokeaha.108.532085

Cited by 178 publications

(187 citation statements)

References 44 publications

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“…Compared with controls, the total number of monocytes was similar in patients on admission and at day 90, but higher at day 2 and at day 7 (Figure 2A), as reported earlier (Urra et al, 2009a). Furthermore, the proportion of CD14 high CD16À monocytes did not change significantly after stroke, but there was a 38% relative increase in CD14 high CD16 + monocytes and a 41% relative decrease in CD14 dim CD16 + monocytes.…”

Section: Monocyte Subtypes and Phenotypesupporting

confidence: 82%

“…Earlier studies have shown that poor outcome after stroke is associated with innate responses signaled through TLR4 in monocytes (Urra et al, 2009a;Yang et al, 2008). In this study, the expression of TLR4 disclosed no significant differences between monocyte subtypes, suggesting that other differences in monocyte subtypes affect stroke outcome.…”

Section: Figurecontrasting

confidence: 44%

“…Stroke may also induce monocyte deactivation, which is characterized by decreased HLA-DR expression and impaired production of proinflammatory cytokines on stimulation with lipopolysaccharide (Emsley et al, 2007;Haeusler et al, 2008). A higher expression of Toll-like receptor (TLR)4 in monocytes of patients with acute stroke was recently associated with poor prognosis (Urra et al, 2009a;Yang et al, 2008), in agreement with experimental data showing that TLR4-deficient mice have minor infarctions and less inflammatory response after an ischemic insult (Caso et al, 2007).…”

Section: Introductionmentioning

confidence: 59%

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Monocyte Subtypes Predict Clinical Course and Prognosis in Human Stroke

Urra

Villamor

Amaro

et al. 2009

J Cereb Blood Flow Metab

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182

164

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The number of circulating monocytes increases after stroke. In this study, we assessed the time course and phenotype of monocyte subsets and their relationship with the clinical course and outcome in 46 consecutive stroke patients and 13 age-matched controls. The proportion of the most abundant 'classical' CD14 high CD16À monocytes did not change after stroke, whereas that of CD14 high CD16 + monocytes increased and CD14 dim CD16 + monocytes decreased. CD14 high CD16 + monocytes had the highest expression of TLR2, HLA-DR and the angiogenic marker, Tie-2; CD14 dim CD16 + monocytes had the highest expression of costimulatory CD86 and adhesion molecule CD49d. Platelet-monocyte interactions were highest in CD14 high CD16À monocytes and lowest in CD14 dim CD16 + monocytes. In adjusted models, 1/CD14 high CD16À monocytes were associated with poor outcome (OR: 1.38), higher mortality (OR: 1.40) and early clinical worsening (OR: 1.29); 2/CD14 high CD16 + monocytes were inversely related to mortality (OR: 0.32); and 3/CD14 dim CD16 + monocytes were inversely related to poor outcome (OR: 0.74) and infarction size (r = À0.45; P = 0.02). These results illustrate that the predominant monocyte subtype conveys harmful effects after stroke, which include stronger interaction with platelets. Alternatively, rarer subpopulations of monocytes are beneficial with a phenotype that could promote tissue repair and angiogenesis. Therefore, monitoring of monocyte subtypes may emerge as a useful tool at the bedside for stroke patients.

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Section: Monocyte Subtypes and Phenotypesupporting

confidence: 82%

Section: Figurecontrasting

confidence: 44%

Section: Introductionmentioning

confidence: 59%

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Monocyte Subtypes Predict Clinical Course and Prognosis in Human Stroke

Urra

Villamor

Amaro

et al. 2009

J Cereb Blood Flow Metab

Self Cite

182

164

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“…As would be expected, the peripheral systemic inflammatory response, evidenced by plasma CRP concentrations and peripheral white-blood counts, is exaggerated in patients with infection, compared to those without (Emsley et al 2003;Fassbender et al 1997). In contrast to the elevated plasma concentrations of inflammatory markers in acute concentrations in the acute phase were associated with stroke-associated infections independent of stroke severity and age (Urra et al 2009). However, in another study, induction of TNF and monocytic HLA-DR expression were associated with incident infections, but these relationships were not independent of infarct volume (Hug et al 2009).…”

Section: Inflammation and Outcome Following Ischemic Strokementioning

confidence: 92%

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Smith

Lawrence

Rodriguez‐Grande

et al. 2013

J Neuroimmune Pharmacol

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Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome.Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infectionsimilar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches.

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“…The number of monocytes is elevated in patients with severe stroke or stroke associated infection. Stroke associated infection may result from the immunosuppressive and anti-inflammatory effects of corticoids, catecholamines, IL-10 and deactivated monocytes [24]. IL-1β expression by HIV infected cells may be one of the important factors for induction of HIV encephalitis.…”

mentioning

confidence: 99%

Cytokines and their Role in Health and Disease: A Brief Overview

Gulati¹,

Guhathakurta²,

Joshi³

et al. 2016

MOJI

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Cytokines are small, non-structural proteins with low molecular weights which have a complex regulatory influence on inflammation and immunity. It has long been considered that development of immune and inflammatory response involves hematopoietic cells, lymphoid cell, and various pro-inflammatory and anti-inflammatory cells, and cytokines mediate the complex interactions of these cells. Cytokines are the intercellular messengers in the immune system where they integrate function of several cell types in various body compartments into a coherent immune response. They have evolved over the years and now include the interferons, the interleukins, the chemokine family, mesenchymal growth factors, the tumor necrosis factor family and adipokines. Earlier known as `soluble factors`, cytokines are produced by and elicit a response from every cell, with the lone exception of the red blood cell. In response to various stimulus cytokines are secreted from various cells including white blood cells. Pleiotropism is the hallmark of a cytokine and there are failures and successes of cytokines and related agents as therapeutic agents. In the membrane of target cells they have specific receptors for their signal transduction and regulatory functions. Beyond the innate and adaptive immunity, cytokines has a major role in many diverse functions including immune cell differentiation, inflammation, angiogenesis, tumorigenesis, neurobiology, viral pathogenesis etc. In addition to inflammation, immunity and infections, cytokines have now expanded their domain to atherosclerosis and cancer. Thus, cytokines may be useful biomarkers for health and disease and act as diagnostic, prognostic and therapeutic agents. This review will highlight the impact of cytokines in various physiological actions, pathophysiological states, therapeutics and the complex interactions between brain and immune cells. knowledge has highlighted the complexity and biphasic nature of cytokines -and the same molecule may have beneficial as well as detrimental effects. For example, interferon-γ (IFNγ), which is essential for defense against several intracellular microorganism such as Mycobacterium tuberculosis, is also a major cytokine in the pathogenesis of several autoimmune diseases. IL-2 is needed for the generation of cytotoxic T-cells (CTL) and forms the basis for several vaccines but the same cytokine drives graft versus host disease and limits the success of bone marrow transplantation [5]. Keywords: Cytokine ReceptorsThe cytokines exert various biological effects through receptors present on the membranes of responsive target cells. These receptors have an extracellular domain, a cytoplasmic domain and a single membrane spanning domain. There is the presence of conserved amino acid sequence motifs on the extracellular domain and these motifs include four conserved cysteine residues. There is also the presence of two polypeptide chains. One is the cytokine specific α subunit and other is a signal transducing β subunit.The nature of the target cell ...

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

Cited by 178 publications

References 44 publications

Monocyte Subtypes Predict Clinical Course and Prognosis in Human Stroke

Monocyte Subtypes Predict Clinical Course and Prognosis in Human Stroke

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Cytokines and their Role in Health and Disease: A Brief Overview

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