Expression of Tumor Necrosis Factor-Alpha and Intercellular Adhesion Molecule-1 after Focal Cerebral Ischemia in Interleukin-1β Converting Enzyme Deficient Mice

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Abstract
Interleukin-1β (IL-1β) is expressed after cerebral ischemia and blocking its action reduces subsequent ischemic brain injury. However, the mechanisms by which IL-1β affects ischemic brain are not understood. To investigate the role of IL-1β in regulation of tumor necrosis factor-alpha (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) during focal cerebral ischemia, the authors studied mutant mice deficient in the IL-1 converting enzyme (ICE) gene (ICE knockout [KO] mice). Ninety-four adult male ICE KO and wild-type mice underwent 3, 6, 12, and 24 hours of permanent middle cerebral artery occlusion using the suture method. Expression of TNF-α and ICAM-1 protein in ischemic brain was examined using immunohistochemistry and Western blot analysis. Neither ICE KO nor wild-type mice had significant differences in CBF and body temperature measurements during the ischemic procedure. TNF-α expression increased in the ipsilateral hemisphere after 3 hours of occlusion, peaked at 12 hours and decreased at 24 hours of ischemia in both ICE KO and wild-type mice. ICAM-1 immunohistochemistry showed that the number of ICAM-1–positive vessels in the ischemic hemisphere was reduced in ICE KO mice ( P < .05). Western blot analysis showed that ICAM-1 protein expression was significantly attenuated in the ipsilateral hemisphere in the ICE KO mice, which paralleled the immunohistochemistry results, The authors' results indicate that TNF-α expression is increased in both ICE KO and wild-type mice suggesting that TNF-α expression is not related to or upregulated by IL-1β. ICAM-1 expression is significantly reduced in the ICE KO mice suggesting that IL-1β plays an important role in the upregulation of adhesion molecules during focal cerebral ischemia.