Review article
Cytokines and adhesion molecules in stroke and related diseases

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Abstract

Once thought as immunologically naive, cells from the central nervous system have been shown to become immunologically reactive and produce various substances including cytokines and adhesion molecules. Recent investigations have revealed that mRNAs of certain cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6 are expressed in the ischemic brain of the animals. Chemokines including CINC, MCP-1, and MIP-1, as well as adhesion molecules such as ICAM-1. ELAM and P-selectin were also found to be expressed. Although identification of the cells producing these cytokines were often difficult, neurons, endothelia, activated astrocytes and microglia/macrophages were the likely sources. The induction of these molecules in ischemic brain is time-locked and appears to be controlled in a highly regulated manner during the process of ischemic cascade. The functional role, interrelationship, and basic mechanism of action of these molecules are being increasingly recognized, while trials such as antiadhesion antibody molecules, growth factors, and anticytokine antibodies have been successful in reducing the neuronal damage in animals subjected to ischemic injury. Furthermore, changes of certain cytokines or adhesion molecules have been detected in the serum or cerebrospinal fluid of patients with stroke and related diseases suggesting that these molecules play a role in the pathogenesis of human stroke. Understanding of these cytokine-adhesion molecule cascades in the ischemic brain may allow us to develop new strategies for the treatment of stroke.

References (126)

  • T. Liu et al.

    Cytokine-induced neutrophil chemoattractant mRNA expressed in cerebral ischemia

    Neurose. Lett.

    (1993)
  • M. Minami et al.

    Effects of kainic acid on messenger RNA levels of IL-1β, IL-6, TNFα and LIF in the rat brain

    Biochem. Biophys. Res. Commun.

    (1991)
  • Y. Matsuo et al.

    Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat

    Brain Res.

    (1994)
  • K.T. Poulsen et al.

    TGFβ2 and TGFβ3 are potent survival factors for midbrain dopaminergic neurons

    Neuron

    (1994)
  • S. Rivera et al.

    Interleukin-1 increases basic fibroblast growth factor mRNA expression in adult rat brain and organotypic hippocampal cultures

    Mol. Brain Res.

    (1994)
  • G. Sebire et al.

    Adhesion proteins on human microglial cells and modulation of their expression by IL-1β and TNFα

    Res. Virol.

    (1993)
  • D. Aderka et al.

    IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice

    J. Immunol.

    (1989)
  • Y. Akaneya et al.

    In vitro model of hypoxia: Basic fibroblast growth factor can rescue cultured CNS neurons from oxygen-deprived cell death

    J. Cereb. Blood Flow Metab.

    (1993)
  • F. Aloisi et al.

    Astrocyte cultures from human embryonic brain: characterization and modulation of surface molecules by inflammatory cytokines

    J. Neurosci. Res.

    (1992)
  • F. Aloisi et al.

    Production of hemolymphopoietic cytokines (IL-6, IL-8, colonytimulating factors) by normal human astrocytes in response to IL-1β and tumor necrosis factor-a

    J. Immunol.

    (1992)
  • S.F. Ameriso et al.

    Immunohematologic characteristics of infection-associated cerebral infarction

    Stroke

    (1991)
  • F.C. Barone et al.

    Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification

    J. Neurosci. Res.

    (1991)
  • F.C. Barone et al.

    Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia

    Stroke

    (1992)
  • N.B. Beamer et al.

    Interleukin-6 and interleukin-1 receptor antagonist in acute stroke

    Ann. Neurol.

    (1995)
  • D. Beasley et al.

    Interleukin-1 induces prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells

    J. Clin. Invest.

    (1991)
  • E.N. Benveniste

    Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action

    Am. J. Physiol.

    (1992)
  • A.L. Betz et al.

    Attenuation of stroke size in rats using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist in brain

    J. Cereb. Blood Flow Metab.

    (1995)
  • M.P. Bevilacqua et al.

    Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines

    J. Clin. Invest.

    (1985)
  • M.P. Bowes et al.

    Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy

    Neurology

    (1995)
  • D.E. Brenneman et al.

    Cytokine regulation of neuronal survival

    J. Neurochem.

    (1992)
  • B. Cannella et al.

    The adhesion molecule and cytokine profile of multiple sclerosis lesions

    Ann Neurol.

    (1995)
  • F. Carey et al.

    A fragment of lipocortin-1 modifies the pyrogenic actions of cytokines in the rat

    Am. J. Physiol.

    (1990)
  • H. Chen et al.

    Anti-CD 11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat

    Ann. Neurol.

    (1994)
  • Chopp, M., Zhang, R.L., Chen, H., Li, Y., Jiang, N., and Rusche, J.R. Postischemic administration of an anti-Mac-1...
  • I.L. Chung et al.

    Tumor necrosis factor production by astrocytes: Induction by lipopolysacharide, IFN-γ, and IL-1β

    J. Immunol.

    (1990)
  • W.M. Clark et al.

    Circulating intercellular adhesion molecule-1 levels and neutrophil adhesion in stroke

    J. Neuroimmunol.

    (1993)
  • W.M. Clark et al.

    Reduction of central nervous system ischemic injury by monoclonal antibody to intercellular adhesion molecule

    J. Neurosurg.

    (1991)
  • M.O. Dereski et al.

    Focal cerebral ischemia in the rat: temporal profile of neutrophil responses

    Neurosci. Res. Commun.

    (1992)
  • G.M. de Courten-Myers et al.

    Efficacious experimental stroke treatment with high dose methylprednisolone

    Stroke

    (1994)
  • F.S. De Giobine et al.

    Interleukin 1: the first interleukin

    Immunol. Today

    (1990)
  • N. Di Julio et al.

    Interleukin-1 beta increases intracellular calcium and alters the electrophysiology of cultured cerebellar purkinje neurons

    Soc. Neurosci.

    (1991)
  • P. Dore-Duffy et al.

    Cytokinemediated activation of cultured CNS microvessels: A system for examining antigenic modulation of CNS endothelial cells, and evidence for long-term expression of the adhesion protein E-selectin

    J. Cereb. Blood Flow Metab.

    (1994)
  • K. Fassbender et al.

    Circulating selectin and immunoglobulin type adhesion molecules in acute ischemic stroke

    Stroke

    (1995)
  • R.A. Fava et al.

    Transforming growth factor 1 induced neutrophil recruitment to synovial tissues: implications for TGF1-driven synovial inflammation and hyperplasia

    J. Exp. Med.

    (1991)
  • Y. Fong et al.

    Antibodies to cachectin/TNF reduce interleukin-1 beta and interleukin-6 appearance during lethal bacteremia

    J. Exp. Med.

    (1989)
  • K. Frei et al.

    Production of macrophage colony-stimulating factor by astrocytes and brain macrophages

    J. Neuroimmunol.

    (1992)
  • M. Freider et al.

    Cultured sympathetic neurons synthesize and release the cytokine interleukin-1b

  • E.M. Frohman et al.

    Astrocytes and intracerebral immune responses

    J. Clin. Immunol.

    (1989)
  • J.R. Gamble et al.

    Transforming growth factor-b inhibits E-selectin expression on human endothelial cells

    J. Immunol.

    (1993)
  • J.H. Garcia et al.

    Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat)

    Am. J. Pathol.

    (1994)
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    Department of Neurology, Asan Medical Center, Song-Pa, PO Box 145, Seoul 138-600, South Korea. Tel: +82-2-224-3442; Fax: +82-2-474-4691.

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