Preferences help
enabled [disable] Abstract
Number of results
2013 | 60 | 3 | 345-349
Article title

Relationship between the induction of inflammatory processes and infectious diseases in patients with ischemic stroke

Title variants
Languages of publication
Pro-inflammatory cytokines participate in the induction of ischemic stroke. So far, their participation in the cerebral ischemia was proven for the tumor necrosis factor TNF-α, interleukin-1 (IL-1), and interleukin-6 (IL-6). The release of the pro-inflammatory cytokines into the extracellular space causes the enlargement of the brain damage region, and consequently increases the neurological deficit and negatively affects the survival rate prognoses. That is confirmed by the increased concentration of pro-inflammatory cytokines in blood and the cerebrospinal fluid of patients with brain stroke, as well as by the research on the induced/experimental cerebral ischemia in animals. The pro-inflammatory cytokines participate in the migration of the reactive T lymphocytes to the regions of brain ischemia where they enhance the nerve tissue damage by down-regulation of microcirculation, induce the pro-thrombotic processes and release other neurotoxic cytokines. Also, in the early stage of cerebral ischemia, cytokines activate the axis hypothalamus-pituitary gland-adrenal cortex and increase the cortisol concentration in blood, what results in the decreased resistance to infectious diseases. Administration of the inhibitor of the interleukin-1 receptor (IL-1Ra) inhibits the inflammatory processes in the region of brain ischemia, and subsequently improves the prognosis for the size of the neurological deficit and the survival rate, as well as resistance to infectious diseases.
Physical description
  • Nerology Department, Regional Polyclinical Hospital in Toruń, Toruń, Poland
  • Department of Crystal Chemistry and Biocrystallography, Nicolaus Copernicus University in Toruń, Toruń, Poland
  • Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University in Bydgoszcz, Bydgoszcz, Poland
  • Astrup J, Siesjö BK, Symon L (1981) Thresholds in cerebral ischemia - the ischemic penumbra. Stroke 12: 723-725.
  • Basic Kes VB, Simundic AM, Nicolac N et al. (2008) Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome. Clinical Biochemistry 41: 1330-1334.
  • Becker KJ (1998) Inflammation and acute stroke. Curr Opin Neurol 11: 45-49.
  • Becker KJ (2001) Targeting the central nervous system inflammatory response in ischemic stroke. Curr Opin Neurol 14: 349-353.
  • Benveniste E, Tang L, Law R (1995) Differential regulation of astrocyte TNF-alpha expression by the cytokines TGF-beta, IL-6 and IL-10. Int J Dev Neurosci 13: 341-349.
  • Beridze M, Sanikidze T, Shakarishvili R et al. (2011) Selected acute phase CSF factors in ischemic stroke: findings and prognostic value. BMC Neurol 11: 41.
  • Biber K, Pinto-Duarte A, Wittendrop MC et al. (2008) Interleukin-6 upregulates neuronal adenosine A1 receptors: implications for neuromodulation and neuroprotection. Neuropsychopharmacology 33: 2237-2250.
  • Boutin H, LeFeuvre RA, Horai R et al. (2001) Role of IL-1alpha and IL-1beta in ischemic brain damage. J Neurosci 21: 5528-5534.
  • Clausen BH, Lambertsen KL, Babcock AA et al. (2008) Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice. J Neuroinflammation 5: 46.
  • Clausen BH, Lambertsen KL, Meldgaard M et al. (2005) A quantitative in situ hybridization and polymerase chain reaction study of microglial-macrophage expression of interleukin-1beta mRNA following permanent middle cerebral artery occlusion in mice. Neuroscience 132: 879-892.
  • Conroy SM, Nguyen V, Quina LA et al. (2004) Interleukin-6 produces neuronal loss in developing cerebellar granule neuron cultures. J Neuroimmunol 155: 43-54.
  • Dziewulska D, Mossakowski MJ (2003) Cellular expression of tumor necrosis factor a and its receptors in human ischemic stroke. Clin Neuropathol 22: 35-40.
  • Emsley HC, Smith CJ, Gavin CM et al. (2007) Clinical outcome following acute ischemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC Neurol 7: 5.
  • Emsley HC, Smith CJ, Georgiou RF, Vail A, Hopkins SJ, Rothwell NJ et al. (2005) A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry 76: 1366-1372.
  • Emsley HC, Smith CJ, Tyrrell PJ et al. (2008) Inflammation in acute ischemic stroke and its relevance to stroke critical care. Neurocrit Care 9: 125-138.
  • Fassbender K, Rossol S, Kammer T et al. (1994) Proinflammatory cytokines in serum of patients with acute cerebral ischemia: kinetics of secretion and relation to the extent of brain damage and outcome of disease. J Neurol Sci 122: 135-139.
  • Gertz K, Kronenberg G, Kälin RE, Baldinger T, Werner C, Balkaya M, Eom GD, Hellmann-Regen J, Kröber J, Miller KR, Lindauer U, Laufs U, Dirnagl U, Heppner FL, Endres M (2012) Essential role of interleukin-6 in post-stroke angiogenesis. Brain 135: 1964-1980.
  • Kostulas N, Kivisäkk P, Huang Y, Matusevicius D, Kostulas V, Link H (1998) Ischemic stroke is associated with a systemic increase of blood mononuclear cells expressing interleukin-8 mRNA. Stroke 29: 462-466.
  • Lambertsen KL, Meldgaard M, Ladeby R et al. (2005) A quantitative study of microglial-macrophage synthesis of tumor necrosis factor during acute and late focal cerebral ischemia in mice. J Cereb Blood Flow Metab 25: 119-135.
  • Licata G, Tuttolomondo A, Di Raimondo D, Corrao S, Di Sciacca R, Pinto A (2009) Immuno-inflammatory activation in acute cardio-embolic strokes in comparison with other subtypes of ischaemic stroke. Thromb Haemost 101: 929-937.
  • Maas MB, Furie KL (2009) Molecular biomarkers in stroke diagnosis and prognosis. Biomark Med 3: 363-383.
  • Montaner J, Rovira A, Molina CA et al. (2003) Plasmatic level of neuroinflammatory markers predict the extent of diffusion-weighted image lesions in hyperacute stroke. J Cereb Blood Flow Metab 23: 1403-1407.
  • Nayak A, Kashyap R, Kabra D, Purohit H, Taori G, Daginawala H (2012) Time course of inflammatory cytokines in acute ischemic stroke patients and their relation to inter-alfa trypsin inhibitor heavy chain 4 and outcome. Ann Indian Acad Neurol 15: 181-185.
  • Nayak A, Kashyap R, Purohit H, Kabra D, Taori G, Daginawala H (2009) Evaluation of the inflammatory response in sera from acute ischemic stroke patients by measurement of IL-2 and IL-10. Inflamm Res 58: 687-691.
  • Nelson TE, Netzeband JG, Gruol DL (2004) Chronic interleukin-6 exposure alters metabotropic glutamate receptor-activated calcium signalling in cerebellar Purkinje neurons. Eur J Neurosci 20: 2387-400.
  • Ormstad H, Aass HC, Lund-Sørensen N et al. (2011) Serum levels of cytokines and C-reactive protein in acute ischemic stroke patients, and their relationship to stroke lateralization, type, and infarct volume. J Neurol 258: 677-685.
  • Pizzi M, Sarnico I, Boroni F et al. (2004) Prevention of neuron and oligodendrocyte degeneration by interleukin-6 (IL-6) and IL-6 receptor/IL-6 fusion protein in organotypic hippocampal slices. Mol Cell Neurosci 25: 301-311.
  • Rodriguez-Mercado R, Ford GD, Xu Z, Kraiselburd EN, Martinez MI, Eterović VA, Colon E, Rodriguez IV, Portilla P, Ferchmin PA, Gierbolini L, Rodriguez-Carrasquillo M, Powell MD, Pulliam JV, McCraw CO, Gates A, Ford BD (2012) Acute neuronal injury and blood genomic profiles in a nonhuman primate model for ischemic stroke. Comp Med 62: 427-438.
  • Sairanen T, Carpen O, Karjalainen-Lindsberg ML et al. (2001) Evolution of cerebral tumor necrosis factor-alpha production during human ischemic stroke. Stroke 32: 1750-1758.
  • Singh HV, Pandey A, Shrivastava AK, Raizada A, Singh SK, Singh N (2013) Prognostic value of neuron specific enolase and IL-10 in ischemic stroke and its correlation with degree of neurological deficit. Clin Chim Acta 18: 419: 136-138.
  • Smith C, Emsley H, Udeh Ch et al. (2012) Interleukin-1 receptor antagonist reverses stroke-associated peripheral immune suppression. Cytokine 58: 384-389.
  • Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, del Zoppo GJ, Hallenbeck JM, Rothwell NJ, Hopkins SJ, Tyrrell PJ (2004) Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome. BMC Neurol 4: 2.
  • Sun Y, Lu CJ, Lin CH, Wen LL (2009) Interleukin-1beta is increased in the cerebrospinal fluid of patients with small infarcts. Eur J Neurol 16: 858-863.
  • Switzer J, Sikora A, Ergul A, Waller JL, Hess DC, Fagan SC (2012) Minocycline prevents IL-6 increase after acute ischemic stroke. Transl Stroke Res 3: 363-368.
  • Taga T, Kishimoto T (1997) Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15: 797-819.
  • Tarkowski E, Rosengren L, Blomstrand C, Wikkelso C, Jensen C, Ekholm S, Tarkowski A (1997) Intrathecal release of pro- and anti-inflammatory cytokines Turing stroke. Clin Exp Immunol 110: 492-499.
  • Tarkowski E, Rosengren L, Blomstrand Ch et al. (1995) Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 26: 1393-1398.
  • Tuttolomondo A, Di Raimondo D, di Sciacca R et al. (2008) Inflammatory cytokines in acute ischemic stroke. Curr Pharm Des 14: 3574-3589.
  • Waje-Andreassen U, Kråkenes J, Ulvestad E et al. (2005) IL-6: an early marker for outcome in acute ischemic stroke. Acta Neurol Scand 111: 360-365.
  • Whiteley W, Jackson C, Lewis S, Lowe G, Rumley A, Sandercock P, Wardlaw J, Dennis M, Sudlow C (2009) Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6. PLoS Med 6: e1000145.
  • Yoon J, Lee J, Tweedie D, Mughal M, Chigurupati S, Greig N, Mattson M (2013) 3,6'-dithiothalidomide improves experimental stroke outcome by suppressing neuroinflammation. J Neurosci Res 91: 671-680.
  • Zaremba J, Losy J (2001) Early TNF-alpha levels correlate with ischaemic stroke severity. Acta Neurol Scand 104: 288-295.
  • Zaremba J, Skrobanski P, Losy J (2001) Tumour necrosis factor-alpha is increased in the cerebrospinal fluid and serum of ischaemic stroke patients and correlates with the volume of evolving brain infarct. Biomed Pharmacother 55: 258-263.
  • Zaremba J, Losy J (2004) Cytokiny w klinicznym i doświadczalnym udarze niedokrwiennym mózgu. Neurol Neurochir Pol 38 (Suppl. 1): S57-S62 (in Polish).
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.