Targeting Interleukin 15 protects brain from cerebral ischemia-reperfusion injury
Gilbert Aaron Lee1, Teng-Nan Lin2, Nan-Shih Liao3 1Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; 3Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
Acute stroke is followed by a complex interplay between the brain and the immune system; in which ischemia-reperfusion leads to detrimental inflammatory response that causes brain injury. Ischemia-reperfusion induces high expression of IL-15 by astrocytes. Transgenic over-expression of IL-15 in astrocyte aggravates the damage of the ischemia-reperfusion brain via promoting the level and the effector function of CD8+ T and NK cells. Treatment of neonatal rat with IL-15 neutralizing antibody before hypoxia-ischemia induction reduces the infarct volume. As stroke-induced inflammatory responses differ between neonate and adult brain, the effects of IL-15 blockade on the injury and immune response of ischemia-reperfusion brain in adult animal remain unclear. In this study, we evaluated the effect of post-ischemia IL-15 neutralizing antibody treatment in cerebral ischemia/reperfusion mice.We found that Il15-/- mice showed smaller infarct size and lower number of activated brain-infiltrating NK cells, CD8+ T cell, and CD4+ T cells in comparison to WT mice after cerebral ischemia-reperfusion. We also found that post-ischemia treatment with IL-15 neutralizing antibody reduces the infarct size and improves the motor and locomotor activity of mice suffered from cerebral ischemia-reperfusion. Furthermore, IL-15 antibody treatment reduces the effector function of NK cells, CD8+ T cells, and CD4+ T cells in the ischemia-reperfusion brain of WT mice. This study demonstrates that ablation of IL-15 response protects the brain injury after cerebral ischemia-reperfusion. Therefore, targeting IL-15 is a potential effective therapy for ischemic stroke.
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