TY - JOUR
T1 - Elevated intracranial il-18 and evidence of neuroprotective effects of IL-18 binding protein (IL-18bp) after experimental closed head injury
AU - Stahel, P. P.
AU - Yatsiv, I.
AU - Morganti-Kossmann, M. C.
AU - Ferez, D.
AU - Novick, D.
AU - Rubinstein, M.
AU - Otto, V. I.
AU - Rancan, M.
AU - Dinarello, C. A.
AU - Shohami, E.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33746370743&partnerID=8YFLogxK
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AN - SCOPUS:33746370743
SN - 1435-2443
VL - 386
SP - 474
EP - 475
JO - Langenbeck's Archives of Surgery
JF - Langenbeck's Archives of Surgery
IS - 6
ER -