Elevated intracranial il-18 and evidence of neuroprotective effects of IL-18 binding protein (IL-18bp) after experimental closed head injury

P. P. Stahel*, I. Yatsiv, M. C. Morganti-Kossmann, D. Ferez, D. Novick, M. Rubinstein, V. I. Otto, M. Rancan, C. A. Dinarello, E. Shohami

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Pro-inflammatory cytokines are important mediators of neuroinflammation after traumatic brain injury. We investigated the posttraumatic release of IL-18 in murine brains following experimental closed head injury (CHI) and in serial human cerebrospinal fluid (CSF) samples of CHI patients. In the murine model, intracerebral IL-18 was induced within 24 hours by simple control procedures, such as ether anesthesia and sham operation. Significantly elevated levels of IL-18 were detected in murine brains at 7 days after CHI and in human CSF samples for up to 10 days after trauma. The intracranial injection of recombinant TNF in normal mice resulted in a significant attenuation of intracerebral IL-18 as compared to mock-injected mice, suggesting that TNF represents an important in vivo mediator of intracerebral IL-18. In order to evaluate the functional aspects of IL-18, mice were injected systemically one hour after trauma with IL-18 binding protein (IL-18BP), a specific inhibitor of IL-18. The IL-18BP-treated mice showed a significantly improved neurological recovery by 7 days compared to vehicletreated animals. In addition, intracerebral IL-18 was attenuated in IL-18BP-injected mice by 7 days, demonstrating that improved recovery was associated with inhibition of IL-18. However, the extent of cerebral edema at 24 hours was not influenced by IL-18BP administration, suggesting that the early detrimental effects of intracerebral inflammation are induced by inflammatory mediators others than IL-18.

Original languageEnglish
Pages (from-to)474-475
Number of pages2
JournalLangenbeck's Archives of Surgery
Volume386
Issue number6
StatePublished - 2001
Externally publishedYes

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