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Blood-Brain Barrier Transport of Cytokines: A Mechanism for Neuropathology

GRECC, Veterans Affairs Medical Center-St. Louis & Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, 915 North Grand Blvd., St. Louis, MO 63106, USA.
Current Pharmaceutical Design (Impact Factor: 3.29). 02/2005; 11(8):973-84. DOI: 10.2174/1381612053381684
Source: PubMed

ABSTRACT Cytokines circulating in the blood affect CNS function through a variety of pathways. One of these pathways is by being transported directly across the blood-brain barrier (BBB). Transport of blood-borne cytokines across the BBB is now known to be an operational pathway by which cytokines can directly affect CNS functions. Cytokine transport across the BBB, however, is a complex event. Not all cytokines are transported and, for those which are, transport rates differ among cytokines, among brain regions, with physiological circumstances, and with disease. Here we address some of the major principles and concepts relating to cytokine transport and BBB function which have emerged as important to neuroimmunology and neuropathology.

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    • "The brain was once perceived as an immune-privileged area. Although large in size, cytokines can cross the blood–brain barrier (BBB), a function not shared with inflammatory markers (Banks, 2005). The first identified region through which cytokines cross the BBB was the circumventricular organs (Blatteis et al., 1983). "
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    • "The brain was once perceived as an immune-privileged area. Although large in size, cytokines can cross the blood–brain barrier (BBB), a function not shared with inflammatory markers (Banks, 2005). The first identified region through which cytokines cross the BBB was the circumventricular organs (Blatteis et al., 1983). "
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    • "Numerous studies have investigated alterations in peripheral cytokines in schizophrenia (Kim, 2005; Kim and Maes, 2003; Stober et al., 2009). Although the CNS is isolated from the peripheral immune system by the blood–brain barrier (BBB), it is possible for cytokines to invade the CNS under normal physiological conditions (Banks, 2005). For example, activated maternal pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 can invade the fetal CNS through various pathways (Banks, 2006). "
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    ABSTRACT: Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GR) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the antioxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GR have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation. Copyright © 2015. Published by Elsevier Inc.
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