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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 2  |  Page : 439-440

Proinflammatory Cytokines in Acute Ischemic Stroke: Where are we Now?

1 Unit of Vascular Cerebral Diseases, Department of Neurology, Servicio de Neurología, Barcelona, Catalonia, Spain
2 Library, Hospital Universitari del Sagrat Cor, Universitat de Barcelona, Barcelona, Catalonia, Spain

Date of Submission20-Nov-2020
Date of Decision20-Nov-2020
Date of Acceptance21-Dec-2020
Date of Web Publication24-Apr-2021

Correspondence Address:
Adria Arboix
Unidad de Enfermedades Vasculares Cerebrales, Servicio de Neurología, Hospital Universitari del Sagrat Cor, c/Viladomat 288, 08029 Barcelona, Catalonia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.314537

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How to cite this article:
Arboix A, Sánchez-López MJ. Proinflammatory Cytokines in Acute Ischemic Stroke: Where are we Now?. Neurol India 2021;69:439-40

How to cite this URL:
Arboix A, Sánchez-López MJ. Proinflammatory Cytokines in Acute Ischemic Stroke: Where are we Now?. Neurol India [serial online] 2021 [cited 2021 May 13];69:439-40. Available from:

Clinical predictors of acute stroke severity and in-hospital outcome are mainly related to demographic characteristics (more severe prognosis in very old patients), presence of certain cerebrovascular risk factors (worse prognosis in patients with atrial fibrillation), semiological data (poor clinical relevance in the presence of low level of consciousness, very early seizures or significant neurological deficit at the onset of stroke), stroke subtype (more frequent in-hospital mortality in cardioembolic stroke and less frequent in lacunar infarct), and extent of lesion damage in neuroimaging.[1],[2]

Multiple mechanisms, such as excitotoxicity, oxidative stress, and inflammation, have been considered to explain brain injury caused by cerebral ischemia. Recently, the usefulness of the different serum biomarkers related to the cascade of inflammatory, hemostatic, glial, and neuronal perturbations has been studied and, among them, the role of proinflammatory cytokines in the clinical relevance of acute ischemic stroke and its correlation with severity and hospital evolution of stroke.[3]

Increasing evidence shows, in experimental models and clinical association, that neuroinflammation promotes further injury that causes cell death since inflammation generates the formation of edema and may favor apoptosis. After inflammation occurs in the brain, it intensifies the discharge of multiple cytokines in both damaged cerebral tissue and peripheral blood. In the literature, some reports indicate that these cytokines with proinflammatory action (such as interleukin-6 and Tumor Necrosis Factor (TNF)-α) are primarily responsible for the onset of the postischemic inflammatory cascade and are involved in the progression of cerebral infarct and influence the severity and outcome of the disease.[4] Increased concentrations in both cerebrospinal fluid and serum have been associated with aggravated neurological symptoms, a larger infarct size, and a worse prognosis.

It is in this line of clinical research referring to the critical role of inflammation in the development of acute ischemic stroke that the study published in this issue of Neurology India is inserted.[5] The authors conducted a cross-sectional, hospital-based, observational study to assess the usefulness of proinflammatory cytokines in acute ischemic stroke and their correlation with stroke severity and hospital outcome. They concluded, in concordance with a considerable number of previous studies, that serum levels of IL-6 and TNF-α were elevated in acute ischemic stroke patients compared to healthy adults and that there was a significant positive correlation between IL-6 and TNF-α with stroke severity assessed by NIHSS score and infarct volume. Furthermore, the level of IL-6 at baseline was also a significant predictor of in-hospital outcome.

However, it should be taken into account that TNF-α and IL-6 also play a role in protecting the cerebral parenchyma from the damage caused by an ischemic stroke in the successive ischemic stages. Consequently, these biomarkers appear to have a bivalent action on brain inflammation that follows the early stages of ischemic brain injury; in fact, they play a proinflammatory role during the first step of the inflammation in the central nervous system, and an immunosuppressive and neurotropic role during the chronic phase.[6] However, at this time little is known about these intriguing correlations.

Furthermore, accumulated evidence shows that there is a delicate balance between proinflammatory and anti-inflammatory cytokines (example: interleukin-10) during the early stages of stroke; the loss of this balance in favor of inflammation results in more severe neurological symptomatology.[7]

Therefore, inflammatory cytokines are involved in the spread of damage and cause apoptosis in the cells of the periphery of ischemic lesions. High levels of proinflammatory cytokines and low levels of anti-inflammatory cytokines are associated with infarct progression, some degree of neurological deficit, clinical worsening, and stroke outcome.[8]

In summary, growing evidence supports the fact that ischemic stroke severity and infarct volume are related to the inflammatory response, so that inflammation during cerebral ischemic could be a promising target in the development of new neuroprotective therapies. However, in the process, cytokines play a bivalent role. Future studies are needed to accurately analyze the anti-inflammatory strategies with the aim of reducing phlogosis and proinflammatory action, even combined with rtPA or thrombectomy to improve the outcome of patients affected by an acute ischemic stroke. More well-designed trials are needed to delineate the associations between these biomarkers and clinical outcomes. Pharmacologic modulation of the inflammatory response may provide the basis for new acute neuroprotective therapies.

  References Top

Arboix A, Alió J. Acute cardioembolic stroke: An update. Expert Rev Cardiovasc Ther 2011;9:367-79.  Back to cited text no. 1
Arboix A, Alvarez-Sabin J, Soler L. [Stroke. Classification and diagnostic criteria. Ad hoc Editorial Committee of theTaskForce on Cerebrovascular Diseases of SEN]. Neurologia 1998;13(Suppl 3):3-10.  Back to cited text no. 2
Maida CD, Norrito RL, Daidone M, Tuttolomondo A, Pinto A. Neuroinflammatory mechanisms in ischemic stroke: Focus on cardioembolic stroke, background, and therapeutic approaches. Int J Mol Sci 2020;21:6454.  Back to cited text no. 3
Bustamante A, López-Cancio E, Pich S, Penalba A, Giralt D, García-Berrocoso T, et al. Blood biomarkers for the early diagnosis of stroke. The Stroke-Chip study. Stroke 2017;48:2419-25.  Back to cited text no. 4
Sangeeta J, Smita M, Anita R. Study of proinflammatory cytokines in acute ischemic stroke and their correlation with stroke severity and in-hospital outcome. Neurol India [In press].  Back to cited text no. 5
Maas MB, Furie K. Molecular biomarkers in stroke diagnosis and prognosis. Biomark Med 2009;3:363-83.  Back to cited text no. 6
Feng L, Guo J, Ai F. Circulating long noncoding RNA ANRIL down regulation correlates with increased risk, higher disease severity and elevated pro-inflammatory cytokines in patients with acute ischemic stroke. J Clin Lab Anal 2019;33:e22629. doi: 10.1002/jcla.22629.  Back to cited text no. 7
Chen Y, Pu J, Liu Y, Tian L, Chen X, Gui S, et al. Pro-inflammatory cytokines are associated with the development of post-stroke depression in the acute stage of stroke: A meta-analysis. Top Stroke Rehabil 2020;27:620-9.  Back to cited text no. 8


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