Skip to main content


Log in

Glial Expression of Interleukin-18 and its Receptor After Excitotoxic Damage in the Mouse Hippocampus

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript


Interleukin (IL)-18, a member of the IL-1 cytokine family, is an important mediator of peripheral inflammation and host defence responses. However, although IL-1 is a key proinflammatory cytokine in the brain, little is known about IL-18 changes in glial cells under excitotoxic neurodegeneration. In this study, we characterized the expressions of IL-18 and IL-18 receptor (IL-18R) in kainic acid (KA)-induced excitotoxicity in mouse hippocampus by immunohistochemistry and Western blotting. IL-18 immunoreactivity was found in microglia whereas IL-18R immunoreactivity was observed in astrocytes. Levels of IL-18 and IL-18R in hippocampus homogenates increased progressively from day 1 post-KA and peaked at 3 days. This study demonstrates the cellular sources of IL-18 and IL-18R, and their temporal correlations after KA-insult, and suggests roles for IL-18 and IL-18R in glial cells in response to excitotoxic damage in the hippocampus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others


  1. Andre R, Wheeler RD, Collins PD et al (2003) Identification of a truncated IL-18R beta mRNA: a putative regulator of IL-18 expressed in rat brain. J Neuroimmunol 145:40–45

    Article  PubMed  CAS  Google Scholar 

  2. Cannella B, Raine CS (2004) Multiple sclerosis: cytokine receptors on oligodendrocytes predict innate regulation. Ann Neurol 55:46–57

    Article  PubMed  CAS  Google Scholar 

  3. Culhane AC, Hall MD, Rothwell NJ et al (1998) Cloning of rat interleukin-18 cDNA. Mol Psychiatry 3:362–366

    Article  PubMed  CAS  Google Scholar 

  4. De Simoni MG, Perego C, Ravizza T et al (2000) Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci 12:2623–2633

    Article  PubMed  Google Scholar 

  5. French AR, Holroyd EB, Yang L et al (2006) IL-18 acts synergistically with IL-15 in stimulating natural killer cell proliferation. Cytokine 35:229–234

    Article  PubMed  CAS  Google Scholar 

  6. Fukui O, Kinugasa Y, Fukuda A et al (2006) Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain. Brain Res 1121:35–45

    Article  PubMed  CAS  Google Scholar 

  7. Gracie JA, Robertson SE, McInnes IB (2003) Interleukin-18. J Leukoc Biol 73:213–224

    Article  PubMed  CAS  Google Scholar 

  8. Hedtjärn M, Leverin AL, Eriksson K et al (2002) Interleukin-18 involvement in hypoxic-ischemic brain injury. J Neurosci 22:5910–5919

    PubMed  Google Scholar 

  9. Hedtjärn M, Mallard C, Arvidsson P et al (2005) White matter injury in the immature brain: role of interleukin-18. Neurosci Lett 373:16–20

    Article  PubMed  Google Scholar 

  10. Hodge DL, Subleski JJ, Reynolds DA et al (2006) The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death. J Interferon Cytokine Res 26:706–718

    Article  PubMed  CAS  Google Scholar 

  11. Hwang SY, Jung JS, Kim TH et al (2006) Ionizing radiation induces astrocyte gliosis through microglia activation. Neurobiol Dis 21:457–467

    Article  PubMed  CAS  Google Scholar 

  12. Ito D, Imai Y, Ohsawa K et al (1998) Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57:1–9

    Article  PubMed  CAS  Google Scholar 

  13. Jander S, Stoll G (2001) Interleukin-18 is induced in acute inflammatory demyelinating polyneuropathy. J Neuroimmunol 114:253–258

    Article  PubMed  CAS  Google Scholar 

  14. Jander S, Schroeter M, Stoll G (2002) Interleukin-18 expression after focal ischemia of the rat brain: association with the late-stage inflammatory response. J Cereb Blood Flow Metab 22:62–70

    Article  PubMed  CAS  Google Scholar 

  15. Jeon GS, Park SW, Kim DW et al (2004) Glial expression of the 90-kDa heat shock protein (HSP90) and the 94-kDa glucose-regulated protein (GRP94) following an excitotoxic lesion in the mouse hippocampus. Glia 48:250–258

    Article  PubMed  Google Scholar 

  16. Jung MK, Song HK, Kim KE et al (2006) IL-18 enhances the migration ability of murine melanoma cells through the generation of ROI and the MAPK pathway. Immunol Lett 107(2):125–130

    Article  PubMed  CAS  Google Scholar 

  17. Laursen SE, Belknap JK (1986) Intracerebroventricular injections in mice. Some methodological refinements. J Pharmacol Methods 16:355–357

    Article  PubMed  CAS  Google Scholar 

  18. Menge T, Jander S, Stoll G (2001) Induction of the proinflammatory cytokine interleukin-18 by axonal injury. J Neurosci Res 65:332–339

    Article  PubMed  CAS  Google Scholar 

  19. Mori I, Hossain MJ, Takeda K et al (2001) Impaired microglial activation in the brain of IL-18-gene-disrupted mice after neurovirulent influenza A virus infection. Virology 287:163–170

    Article  PubMed  CAS  Google Scholar 

  20. Nadler JV, Perry BW, Gentry C et al (1980) Degeneration of hippocampal CA3 pyramidal cells induced by intraventricular kainic acid. J Comp Neurol 192:333–359

    Article  PubMed  CAS  Google Scholar 

  21. Nakanishi K, Yoshimoto T, Tsutsui H et al (2001) Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 19:423–474

    Article  PubMed  CAS  Google Scholar 

  22. Prinz M, Hanisch UK (1999) Murine microglial cells produce and respond to interleukin-18. J Neurochem 72:2215–2218

    Article  PubMed  CAS  Google Scholar 

  23. Vezzani A, Moneta D, Conti M et al (2000) Powerful anticonvulsant action of IL-1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc Natl Acad Sci USA 97:11534–11539

    Article  PubMed  CAS  Google Scholar 

  24. Wheeler RD, Culhane AC, Hall MD et al (2000) Detection of the interleukin 18 family in rat brain by RT-PCR. Brain Res Mol Brain Res 77:290–293

    Article  PubMed  CAS  Google Scholar 

  25. Zhang XM, Duan RS, Chen Z et al (2007) IL-18 deficiency aggravates kainic acid-induced hippocampal neurodegeneration in C57BL/6 mice due to an overcompensation by IL-12. Exp Neurol 205:64–73

    Article  PubMed  CAS  Google Scholar 

Download references


This study was supported by the second stage Brain Korea 21 Project in 2007 and a grant (M103KV010018 04K2201 01850) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea. The authors thank Dr. S. Kohsaka, National Institute of Neuroscience, Japan, for the iba1 antibody.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Sa Sun Cho.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jeon, G.S., Park, S.K., Park, S.W. et al. Glial Expression of Interleukin-18 and its Receptor After Excitotoxic Damage in the Mouse Hippocampus. Neurochem Res 33, 179–184 (2008).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: