Title: Inflammatory Cytokines in Acute Ischemic Stroke
Volume: 14
Issue: 33
Author(s): Antonino Tuttolomondo, Domenico Di Raimondo, Riccardo di Sciacca, Antonio Pinto and Giuseppe Licata
Affiliation:
Keywords:
Ischemic Stroke, cytokines, tumor necrosis factor (TNF-α), Neurones, astrocytes, oligodendrocytes, Central Nervous System (CNS)
Abstract: Three major cytokines, namely, tumor necrosis factor (TNF-α), interleukin (IL)-1, and IL-6 are produced by cultured brain cells after various stimuli such as ischemia. Neurones, astrocytes, microglia and oligodendrocytes can produce inflammatory mediators, and cytokine receptors are expressed constitutionally throughout the Central Nervous System (CNS), albeit at low levels. Cytokines are involved in virtually every facet of stroke and they have numerous proinflammatory and pro-coagulant effects on endothelium. TNF-α expression after stroke stimulates expression of tissue factor and adhesion molecules for leukocytes, release of interleukin-1 (IL-1), nitric oxide, factor VIII/von Willebrand factor, platelet-activating factor and endothelin, suppression of the thrombomodulin-protein C-protein S system, reduction of tissue-plasminogen activator and release of plasminogen activator inhibitor-1. Research into the actions of IL-1β in the brain initially focused on its role in host defence responses to systemic disease. IL-1β can also elicit an array of responses which could either inhibit, exacerbate or induce neuronal damage and death. IL-6 can be induced by a variety of molecules including IL-1, TNF-α, transforming growth factor-β and prostaglandins (PGs), and many other mediators such as b-amyloid, interferon-g (IFNg) and IL-4 can potentiate these primary inducers, highlighting the complex nature of IL-6 modulation. Several studies reported that plasma levels of TNF-α and IL-6 are associated with prognosis after ischemic stroke and our group showed that plasma levels of cytokines such as TNF-α, IL-1β are different in every diagnostic subtype of ischemic stroke, and how plasma levels of some immunoinflammatory markers and thrombotic-phybrinolitic markers are predictive of acute ischemic stroke diagnosis in the acute setting.