Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

The role of cytokines in seizures: interleukin (IL)-$1{\beta}$, IL-1Ra, IL-8, and IL-10

  • Youn, Youngah (Department of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Sung, In Kyung (Department of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Lee, In Goo (Department of Pediatrics, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine)
  • Received : 2013.02.15
  • Accepted : 2013.04.01
  • Published : 2013.07.15
Download PDF
⟨ Previous Next ⟩

Abstract

Brain insults, including neurotrauma, infection, and perinatal injuries such as hypoxic ischemic encephalopathy, generate inflammation in the brain. These inflammatory cascades induce a wide spectrum of cytokines, which can cause neuron degeneration, have neurotoxic effects on brain tissue, and lead to the development of seizures, even if they are subclinical and occur at birth. Cytokines are secreted by the glial cells of the central nervous system and they function as immune system mediators. Cytokines can be proinflammatory or anti-inflammatory. Interleukin (IL)-$1{\beta}$ and IL-8 are proinflammatory cytokines that activate additional cytokine cascades and increase seizure susceptibility and organ damage, whereas IL-1 receptor antagonist and IL-10 act as anti-inflammatory cytokines that have protective and anticonvulsant effects. Therefore, the immune system and its associated inflammatory reactions appear to play an important role in brain damage. Whether cytokine release is relevant for the processes of epileptogenesis and antiepileptogenesis, and whether epileptogenesis could be prevented by immunomodulatory treatment should be addressed in future clinical studies. Furthermore, early detection of brain damage and early intervention are essential for the prevention of disease progression and further neurological complications. Therefore, cytokines might be useful as biomarkers for earlier detection of brain damage in high-risk infants.

Keywords

References

  1. Vezzani A, Granata T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 2005;46:1724-43. https://doi.org/10.1111/j.1528-1167.2005.00298.x
  2. Vezzani A, Balosso S, Ravizza T. The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 2008;22:797-803. https://doi.org/10.1016/j.bbi.2008.03.009
  3. UpToDate. Role of cytokines in the immune system [Internet]. Waltham: UpToDate Inc., c2013 [cited 2013 Jan 1]. Available from: http://www.uptodate.com/contents/role-of-cytokines-in-theimmune-system.
  4. Li G, Bauer S, Nowak M, Norwood B, Tackenberg B, Rosenow F, et al. Cytokines and epilepsy. Seizure 2011;20:249-56. https://doi.org/10.1016/j.seizure.2010.12.005
  5. Sinha S, Patil SA, Jayalekshmy V, Satishchandra P. Do cytokines have any role in epilepsy? Epilepsy Res 2008;82:171-6. https://doi.org/10.1016/j.eplepsyres.2008.07.018
  6. Dembinski J, Behrendt D, Martini R, Heep A, Bartmann P. Modulation of pro- and anti-inflammatory cytokine production in very preterm infants. Cytokine 2003;21:200-6. https://doi.org/10.1016/S1043-4666(02)00498-2
  7. Liu Z, Holmes GL. Basic fibroblast growth factor-induced seizures in rats. Neurosci Lett 1997;233:85-8. https://doi.org/10.1016/S0304-3940(97)00627-7
  8. Cuevas P, Gimenez-Gallego G. Antiepileptic effects of acidic fibroblast growth factor examined in kainic acid-mediated seizures in the rat. Neurosci Lett 1996;203:66-8. https://doi.org/10.1016/0304-3940(95)12254-0
  9. Volpe JJ. Perinatal brain injury: from pathogenesis to neuroprotection. Ment Retard Dev Disabil Res Rev 2001;7:56-64. https://doi.org/10.1002/1098-2779(200102)7:1<56::AID-MRDD1008>3.0.CO;2-A
  10. Tan S, Zhou F, Nielsen VG, Wang Z, Gladson CL, Parks DA. Sustained hypoxia-ischemia results in reactive nitrogen and oxygen species production and injury in the premature fetal rabbit brain. J Neuropathol Exp Neurol 1998;57:544-53. https://doi.org/10.1097/00005072-199806000-00002
  11. de Vries HE, Blom-Roosemalen MC, van Oosten M, de Boer AG, van Berkel TJ, Breimer DD, et al. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol 1996;64:37-43. https://doi.org/10.1016/0165-5728(95)00148-4
  12. Wong D, Dorovini-Zis K, Vincent SR. Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model of the human blood-brain barrier. Exp Neurol 2004;190:446-55. https://doi.org/10.1016/j.expneurol.2004.08.008
  13. Candelario-Jalil E, Taheri S, Yang Y, Sood R, Grossetete M, Estrada EY, et al. Cyclooxygenase inhibition limits blood-brain barrier disruption following intracerebral injection of tumor necrosis factoralpha in the rat. J Pharmacol Exp Ther 2007;323:488-98. https://doi.org/10.1124/jpet.107.127035
  14. UpToDate. Etiology and pathogenesis of neonatal encephalopathy [Internet]. Waltham: UpToDate Inc., c2013 [cited 2013 Jan 1]. Available from: http://www.uptodate.com/contents/etiology-andpathogenesis-of-neonatal-encephalopathy.
  15. Dinarello CA, Novick D, Puren AJ, Fantuzzi G, Shapiro L, Muhl H, et al. Overview of interleukin-18: more than an interferon-gamma inducing factor. J Leukoc Biol 1998;63:658-64. https://doi.org/10.1002/jlb.63.6.658
  16. Ravizza T, Vezzani A. Status epilepticus induces time-dependent neuronal and astrocytic expression of interleukin-1 receptor type I in the rat limbic system. Neuroscience 2006;137:301-8. https://doi.org/10.1016/j.neuroscience.2005.07.063
  17. Youn YA, Kim SJ, Sung IK, Chung SY, Kim YH, Lee IG. Serial examination of serum IL-8, IL-10 and IL-1Ra levels is significant in neonatal seizures induced by hypoxic-ischaemic encephalopathy. Scand J Immunol 2012;76:286-93. https://doi.org/10.1111/j.1365-3083.2012.02710.x
  18. Kanemoto K, Kawasaki J, Yuasa S, Kumaki T, Tomohiro O, Kaji R, et al. Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion. Epilepsia 2003;44:796-9. https://doi.org/10.1046/j.1528-1157.2003.43302.x
  19. Virta M, Hurme M, Helminen M. Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures. Pediatr Neurol 2002;26:192-5. https://doi.org/10.1016/S0887-8994(01)00380-0
  20. Peltola J, Palmio J, Korhonen L, Suhonen J, Miettinen A, Hurme M, et al. Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures. Epilepsy Res 2000;41:205-11. https://doi.org/10.1016/S0920-1211(00)00140-6
  21. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996;87:2095-147.
  22. Vezzani A, Moneta D, Richichi C, Aliprandi M, Burrows SJ, Ravizza T, et al. Functional role of inflammatory cytokines and antiinflammatory molecules in seizures and epileptogenesis. Epilepsia 2002;43 Suppl 5:30-5. https://doi.org/10.1046/j.1528-1157.43.s.5.14.x
  23. De Simoni MG, Perego C, Ravizza T, Moneta D, Conti M, Marchesi F, et al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci 2000;12:2623-33. https://doi.org/10.1046/j.1460-9568.2000.00140.x
  24. Asano T, Ichiki K, Koizumi S, Kaizu K, Hatori T, Fujino O, et al. IL-8 in cerebrospinal fluid from children with acute encephalopathy is higher than in that from children with febrile seizure. Scand J Immunol 2010;71:447-51. https://doi.org/10.1111/j.1365-3083.2010.02391.x
  25. Kossmann T, Stahel PF, Lenzlinger PM, Redl H, Dubs RW, Trentz O, et al. Interleukin-8 released into the cerebrospinal fluid after brain injury is associated with blood-brain barrier dysfunction and nerve growth factor production. J Cereb Blood Flow Metab 1997;17:280-9. https://doi.org/10.1097/00004647-199703000-00005
  26. Whalen MJ, Carlos TM, Kochanek PM, Wisniewski SR, Bell MJ, Clark RS, et al. Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med 2000;28:929-34. https://doi.org/10.1097/00003246-200004000-00003
  27. Tan S, Parks DA. Preserving brain function during neonatal asphyxia. Clin Perinatol 1999;26:733-47.

Cited by

  1. Interleukin-6 and Interleukin-8 Levels Correlate With the Severity of Aplastic Anemia in Children vol.39, pp.3, 2013, https://doi.org/10.1097/mph.0000000000000724
  2. Analysis of plasma multiplex cytokines and increased level of IL-10 and IL-1Ra cytokines in febrile seizures vol.14, pp.None, 2013, https://doi.org/10.1186/s12974-017-0974-7
  3. Anticancer agent 6-MITC at extremely low dosage can control seizures by stabilizing membrane excitability system in mutant EL mice vol.10, pp.1, 2013, https://doi.org/10.3805/eands.10.44
  4. Cerebrospinal Fluid Protein Changes in Preeclampsia vol.72, pp.1, 2013, https://doi.org/10.1161/hypertensionaha.118.11153
  5. Glial cells, blood brain barrier and cytokines in seizures: Implications for therapeutic modalities vol.69, pp.3, 2018, https://doi.org/10.5937/mp69-18143
  6. Advances in the Potential Biomarkers of Epilepsy vol.10, pp.None, 2013, https://doi.org/10.3389/fneur.2019.00685
  7. Association of Tumor Necrosis Factor-α Gene Promotor Variant, Not Interleukin-10, with Febrile Seizures and Genetic Epilepsy with Febrile Seizure Plus vol.27, pp.2, 2013, https://doi.org/10.26815/acn.2019.00038
  8. Interleukin-10 inhibits interleukin-1β production and inflammasome activation of microglia in epileptic seizures vol.16, pp.None, 2013, https://doi.org/10.1186/s12974-019-1452-1
  9. The effect of omega-3 fatty acids on clinical and paraclinical features of intractable epileptic patients: a triple blind randomized clinical trial vol.8, pp.1, 2019, https://doi.org/10.1186/s40169-019-0220-2
  10. Intrathecal Infusion of Autologous Adipose-Derived Regenerative Cells in Autoimmune Refractory Epilepsy: Evaluation of Safety and Efficacy vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/7104243
  11. The Pathogenesis of Nodding Syndrome vol.15, pp.1, 2020, https://doi.org/10.1146/annurev-pathmechdis-012419-032748
  12. The Effect of β-d-Mannuronic Acid in Animal Model of Epilepsy vol.15, pp.4, 2020, https://doi.org/10.1177/1934578x20920030
  13. Cytokines and neuron-specific proteins in pediatric viral encephalitis and convulsive syndrome. I. Viral encephalitis vol.10, pp.4, 2013, https://doi.org/10.15789/2220-7619-can-1448
  14. Effects of prednisolone on behavioral and inflammatory profile in animal model of PTZ-induced seizure vol.743, pp.None, 2021, https://doi.org/10.1016/j.neulet.2020.135560
  15. Metformin ameliorates the status epilepticus- induced hippocampal pathology through possible mTOR modulation vol.29, pp.1, 2013, https://doi.org/10.1007/s10787-020-00782-8
  16. Cytokines and Onchocerciasis-Associated Epilepsy, a Pilot Study and Review of the Literature vol.10, pp.3, 2013, https://doi.org/10.3390/pathogens10030310
  17. Induction of Tertiary Phase Epileptiform Discharges after Postasphyxial Infusion of a Toll-Like Receptor 7 Agonist in Preterm Fetal Sheep vol.22, pp.12, 2021, https://doi.org/10.3390/ijms22126593
  18. Nano dot blot: An alternative technique for protein identification and quantification in a high throughput format vol.358, pp.None, 2013, https://doi.org/10.1016/j.jneumeth.2021.109194
  19. Thymoquinone Potentiates the Effect of Phenytoin against Electroshock-Induced Convulsions in Rats by Reducing the Hyperactivation of m-TOR Pathway and Neuroinflammation: Evidence from In Vivo, In Vitr vol.14, pp.11, 2021, https://doi.org/10.3390/ph14111132