Interleukin-18 involvement in hypoxic-ischemic brain injury.

Abstract

Inflammation is a critical factor for development of hypoxic-ischemic (HI) brain injury. Interleukin-18 (IL-18) is a proinflammatory cytokine expressed in microglia and processed by caspase-1. Our aim was to characterize the expression of IL-18 and its receptor in relation to caspase-1 and IL-1beta after HI and to evaluate to what extent IL-18 contributes to HI brain injury. Seven-day-old rats were subjected to HI, and brain tissue was sampled at different time points (3 hr to 14 d) after insult. The mRNA for IL-18 and caspase-1 were analyzed with reverse transcriptase PCR, protein was analyzed by Western blot (IL-18, caspase-1) or ELISA (IL-1beta), and the regional distribution was assessed by immunohistochemistry. HI was also induced in C57BL/6 mice, and brain injury in IL-18-deficient animals was compared with that in wild-type animals. The expression of mRNA/protein for caspase-1 and IL-18 in brain homogenates increased progressively at 12 hr to 14 d after HI, whereas IL-1beta peaked at 8 hr. A widespread expression of caspase-1 and IL-18 protein in microglia was found in the HI hemisphere. The IL-18 receptor was expressed on neurons of the cerebral cortex and thalamus. IL-1beta was primarily found in microglia in the habenular nucleus of the thalamus. The infarct volume was reduced by 21% (p = 0.01), and the neuropathology score was significantly decreased in the cerebral cortex (-35%), hippocampus (-22%), striatum (-18%), and thalamus (-17%) in mice with IL-18 deficiency compared with wild-type mice. In conclusion, we found that IL-18 expression in microglia was markedly increased after HI and that IL-18 appears to be important for the development of HI brain injury.

• Authors: Maj Hedtjärn, Anna-Lena Leverin, Kristina Eriksson, Klas Blomgren, Carina Mallard, Henrik Hagberg
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 22 Issue 14 Pg. 5910-9 (Jul 15 2002) ISSN: 1529-2401 [Electronic] United States
• PMID: 12122053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Il18r1 protein, mouse
• Interleukin-1
• Interleukin-18
• Interleukin-18 Receptor alpha Subunit
• RNA, Messenger
• Receptors, Interleukin
• Receptors, Interleukin-18
• Caspase 1

Topics

• Animals
• Animals, Newborn
• Blotting, Western
• Brain (blood supply, metabolism, pathology)
• Brain Chemistry
• Caspase 1 (genetics, metabolism)
• Disease Models, Animal
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Female
• Hypoxia-Ischemia, Brain (metabolism, pathology)
• Immunohistochemistry
• Interleukin-1 (metabolism)
• Interleukin-18 (deficiency, genetics, metabolism)
• Interleukin-18 Receptor alpha Subunit
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (metabolism, pathology)
• Neurons (metabolism, pathology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Receptors, Interleukin (biosynthesis)
• Receptors, Interleukin-18
• Reverse Transcriptase Polymerase Chain Reaction