1. ^*Pediatric Intensive Care Unit, Hebrew University Hadassah Medical Center, Jerusalem, Israel
2. ^†Department of Pharmacology, Hebrew University Hadassah Medical Center, Jerusalem, Israel
3. ^‡Division of Research and Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, Zurich, Switzerland
4. ^§Department of Trauma Surgery, The Alfred Hospital, Monash University, Prahran Victoria, Australia
5. Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, U.S.A.
6. ^¶Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
7. ^#Department of Visceral and Transplantation Surgery, University of Bern Medical School, Inselspital, Bern, Switzerland
8. ^**Department of Trauma and Reconstructive Surgery, University Hospital Benjamin Franklin, The Free University of Berlin, Berlin, Germany

Correspondence: Esther Shohami, Department of Pharmacology, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel; e-mail: esty@cc.huji.ac.il

¹E.S. is affiliated with the David R. Bloom Center for Pharmacy, The Hebrew University, Jerusalem.

Received 17 January 2002; Revised 16 April 2002; Accepted 17 April 2002.

Abstract

Proinflammatory cytokines are important mediators of neuroinflammation after traumatic brain injury. The role of interleukin (IL)-18, a new member of the IL-1 family, in brain trauma has not been reported to date. The authors investigated the posttraumatic release of IL-18 in murine brains following experimental closed head injury (CHI) and in CSF of CHI patients. In the mouse model, intracerebral IL-18 was induced within 24 hours by ether anesthesia and sham operation. Significantly elevated levels of IL-18 were detected at 7 days after CHI and in human CSF up to 10 days after trauma. Published data imply that IL-18 may play a pathophysiological role in inflammatory CNS diseases; therefore its inhibition may ameliorate outcome after CHI. To evaluate the functional aspects of IL-18 in the injured brain, mice were injected systemically with IL-18–binding protein (IL-18BP), a specific inhibitor of IL-18, 1 hour after trauma. IL-18BP–treated mice showed a significantly improved neurological recovery by 7 days, accompanied by attenuated intracerebral IL-18 levels. This demonstrates that inhibition of IL-18 is associated with improved recovery. However, brain edema at 24 hours was not influenced by IL-18BP, suggesting that inflammatory mediators other than IL-18 induce the early detrimental effects of intracerebral inflammation.