QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (45) Citing Articles via Google Scholar Google Scholar Articles by Touzani, O. Articles by Rothwell, N. Search for Related Content PubMed PubMed Citation Articles by Touzani, O. Articles by Rothwell, N.

 Previous Article  |  Next Article 

The Journal of Neuroscience, January 1, 2002, 22(1):38-43

Interleukin-1 Influences Ischemic Brain Damage in the Mouse Independently of the Interleukin-1 Type I Receptor

Omar Touzani^{*, *}, Herve Boutin^{*, *}, Rosalind LeFeuvre, Lisa Parker, Andy Miller, Giamal Luheshi, and Nancy Rothwell

School of Biological Sciences, University of Manchester, M13 9PT, United Kingdom

The cytokine interleukin-1 (IL-1) contributes to ischemic, excitotoxic, and traumatic brain injury. IL-1 actions depend on interaction with a single receptor (IL-1RI), which associates with an accessory protein (IL-1RAcP), and is blocked by IL-1 receptor antagonist (IL-1ra). Here we show that in normal mice [wild-type (WT)], intracerebroventricular injection of IL-1ra markedly reduces (50%; p < 0.01) ischemic brain damage caused by reversible occlusion of the middle cerebral artery, whereas injection of IL-1 exacerbates damage (+45%; p < 0.05).

Mice lacking IL-1RI [IL-1RI knock-out (KO)] exhibited ischemic brain damage that is almost identical to that of the WT (infarct volume 43.7 ± 6.1 and 46.2 ± 6.2 mm³, respectively), but failed to respond to injection of IL-1ra. However, injection of IL-1 (intracerebroventricularly) exacerbated ischemic brain damage in IL-1RI KO (+61%; p < 0.001) and in WT mice (+45%). This effect of IL-1 was abolished by heat denaturation in all animals, and was reversed by IL-1ra in WT, but not IL-1RI KO mice. In contrast, IL-1RI KO mice were completely resistant to effects of IL-1 on food intake or body weight. IL-1RAcP mRNA was increased by stroke in WT, but reduced in IL-1RI KO mice compared with sham-operated mice. Type II IL-1 receptor mRNA was significantly increased 4 hr after ischemia in WT and IL-1RI KO (+20%) animals.

These data show that IL-1 can exacerbate ischemic brain damage independently of IL-1RI and suggest the existence of additional signaling receptor or receptors for IL-1 in the brain.

Key words: cerebrovascular accident; brain infarction; receptors; interleukin-1; mice; knock-out; cytokines

---

^* O.T. and H.B. contributed equally to this work.

Correspondence should be addressed to Prof. Nancy Rothwell, School of Biological Sciences, 1.124 Stopford Building, University of Manchester, M13 9PT, UK. E-mail: Nancy.Rothwell{at}man.ac.uk.

O. Touzani's present address: Université de Caen-Unité Mixte de Recherche Centre National de la Recherche Scientifique 6551, Centre Cyceron, Boulevard H. Becquerel BP 5229, 14074 Caen, France.

G. Luheshi's present address: The Douglas Hospital Research Center, 6875 Boulevard Lassale, Verdun, Quebec H4R 1R3, Canada.

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22138-06$05.00/0

This article has been cited by other articles:

				T. P. Obrenovitch Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia Physiol Rev, January 1, 2008; 88(1): 211 - 247. [Abstract] [Full Text] [PDF]

				B. Fogal, J. Li, D. Lobner, L. D. McCullough, and S. J. Hewett System xc Activity and Astrocytes Are Necessary for Interleukin-1{beta}-Mediated Hypoxic Neuronal Injury J. Neurosci., September 19, 2007; 27(38): 10094 - 10105. [Abstract] [Full Text] [PDF]

				L. Struzynska, B. Dabrowska-Bouta, K. Koza, and G. Sulkowski Inflammation-Like Glial Response in Lead-Exposed Immature Rat Brain Toxicol. Sci., January 1, 2007; 95(1): 156 - 162. [Abstract] [Full Text] [PDF]

				M. Samardzija, A. Wenzel, M. Thiersch, R. Frigg, C. Reme, and C. Grimm Caspase-1 Ablation Protects Photoreceptors in a Model of Autosomal Dominant Retinitis Pigmentosa Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5181 - 5190. [Abstract] [Full Text] [PDF]

				P. Honore, D. Donnelly-Roberts, M. T. Namovic, G. Hsieh, C. Z. Zhu, J. P. Mikusa, G. Hernandez, C. Zhong, D. M. Gauvin, P. Chandran, et al. A-740003 [N-(1-{[(Cyanoimino)(5-quinolinylamino) methyl]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a Novel and Selective P2X7 Receptor Antagonist, Dose-Dependently Reduces Neuropathic Pain in the Rat J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1376 - 1385. [Abstract] [Full Text] [PDF]

				J. Lazovic, A. Basu, H.-W. Lin, R. P. Rothstein, J. K. Krady, M. B. Smith, and S. W. Levison Neuroinflammation and Both Cytotoxic and Vasogenic Edema Are Reduced in Interleukin-1 Type 1 Receptor-Deficient Mice Conferring Neuroprotection Stroke, October 1, 2005; 36(10): 2226 - 2231. [Abstract] [Full Text] [PDF]

				A. M. Lynch, M. Moore, S. Craig, P. E. Lonergan, D. S. Martin, and M. A. Lynch Analysis of Interleukin-1{beta}-induced Cell Signaling Activation in Rat Hippocampus following Exposure to Gamma Irradiation: PROTECTIVE EFFECT OF EICOSAPENTAENOIC ACID J. Biol. Chem., December 19, 2003; 278(51): 51075 - 51084. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help