Editorial [Hot Topic: Citokines and Inflammation Markers in Ischemic Stroke (Executive Editor: Antonino Tuttolomondo)]

Interest in neuroimmunology and the actions of cytokines in the brain has grown exponentially over the last decade. Cytokines represent a large and rapidly growing group of polypeptides that comprises the interleukins, chemokines, tumor necrosis factors, interferons, and growth and cell stimulating factors [1]. The functions and actions of many of these cytokines in the brain remain to be elucidated, but probably include both beneficial and detrimental effects.. During the course of brain ischemia, inflammatory mechanisms both intrinsic to brain as well as blood are among the important mediators of focal cerebral injury, nevertheless ischemic stroke is a heterogeneous disease, and inflammatory pathways may have different impacts depending on underlying pathophysiological processes [2] . Inflammatory cells such as neutrophils and macrophages infiltrate into the ischemic brain in various animal models of ischemic stroke and in patients with cerebral ischemia [3]. In addition, inherent cells such as astrocytes, microglia, or endothelia have been found to be activated by cerebral injuries including ischemic stroke. These cells then become immunologically reactive and interact with each other by producing substances including cytokines and adhesion molecules. These molecules appear to be responsible for the accumulation of inflammatory cells in the injured brain, and the resulting immunologic-inflammatory cascade produces an environment that may affect the survival of neurons subjected to ischemic injury. Several aspects of this immunologic-inflammatory cascade will be presented in this issue of Current Pharmaceutical Design, in order to put in a better perspective of the inflammatory mechianisms of neuronal damage mechanism, the role of proinflammatory cytokines in acute ischemic stroke, the linkage between proinflammatory genes polymorphism and ischemic stroke and the role of inflammation markers as possible target for a neuroprotective treatment of acute ischemic stroke. TNF-a is activated in experimental ischemia at both the mRNA and protein levels. Furthermore, increased levels of cytokines such as interleukin IL-1β, tumor necrosis factor-α (TNF-α), and IL-6, as well as adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), have been observed after experimental brain ischemia [4]. Clinical studies [5-7] have reported increased levels of proinflammatory cytokines and adhesion molecules in the peripheral blood and cerebrospinal fluid (CSF) of patients with ischemic stroke. Among cytokines involved in pathogenesis of ischemic stroke, high IL-6 concentrations in CSF and plasma have been associated with larger infarct size, neurological deterioration, and poor outcome independently of the stroke subtype [8]. Castellanos [9] et al. showed that in patients with lacunar infarction, high concentrations of inflammatory markers in blood are associated with early neurological deterioration (END) and poor functional outcome in lacunar infarctions. So, cerebral ischemia and inflammation are closely interrelated: ischemia is a robust stimulus for potentially damaging inflammation, and infection and its associated inflammation is a known risk factor for ischemic stroke [10] and inflammation also contributes to ischemic events through the promotion of atherosclerosis [11]. Moreover, functional polymorphisms of inflammatory genes may thereby influence the incidence and outcome of ischemic stroke and recent studies explored the role of IL-6 gene polymorphism [12-14] and of TNF-α polymorphism [15-17] both in acute stroke setting and in subjects with a history of ischemic stroke. On this basis, in acute ischemic stroke setting, cytokines and other markers of inflammation may represent, owing to their pathogenetic and predictive role, a possible therapeutic target and although there are no current clinical ‘anti-cytokine’ treatment studies for stroke, experimental studies modulating IL-1 and TNF-alpha have shown neuroprotection, [18,19] but further studies are needed to confirm this issue, which could open new future therapeutic avenues in the treatment of brain ischemia.