Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1 beta converting enzymedeficient mice

Interleukin-l beta (IL-l beta) is expressed after cerebral ischemia and blo cking its action reduces subsequent ischemic brain injury. However, the mec hanisms by which IL-l beta affects ischemic brain are not understood. To in vestigate the role of IL-l beta in regulation of tumor necrosis factor-alph a (TNF-alpha) and intercellular adhesion molecule-1 (ICAM-1) during focal c erebral ischemia, the authors studied mutant mice deficient in the IL-1 con verting 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 midd le cerebral artery occlusion using the suture method. Expression of TNF-alp ha and ICAM-1 protein in ischemic brain was examined using immunohistochemi stry and Western blot analysis. Neither ICE KO nor wild-type mice had signi ficant differences in CBF and body temperature measurements during the isch emic procedure. TNF-alpha expression increased in the ipsilateral hemispher e 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-l-positive vessels in the ischemic hemispher e was reduced in ICE KO mice (P < .05). Western blot analysis showed that I CAM-1 protein expression was significantly attenuated in the ipsilateral he misphere in the ICE KO mice, which paralleled the immunohistochemistry resu lts. The authors' results indicate that TNF-alpha expression is increased i n both ICE KO and wild-type mice suggesting that TNF-alpha expression is no t related to or upregulated by IL-1 beta. ICAM-1 expression is significantl y reduced in the ICE KO mice suggesting that IL-l beta plays an important r ole in the upregulation of adhesion molecules during focal cerebral ischemi a.