期刊
CYTOKINE
卷 43, 期 1, 页码 54-62出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2008.04.007
关键词
perinatal brain lesions; cerebral palsy; cytokines; ischemia
Bacterial infections and hypoxia/ischemia (H/I) are implicated in human neonatal brain damage leading to cerebral palsy (CP). We developed an animal model presenting similar perinatal brain damage by combining bacterial endotoxin and H/I insults. Interleukin (IL)-1 beta is a mediator of brain damage and its action(s) is counteracted by its cognate anti-inflammatory IL-1 receptor antagonist (IL-1ra). We tested the hypothesis that the balance between agonist and antagonist in the IL-1 system is shifted towards inflammation in perinatal brains exposed to endotoxin and/or H/I Lipopolysaccharide (LPS) and/or H/I enhanced both intracerebral IL-1 beta mRNA and protein levels, with a maximum increase observed with combined LIPS and H/I insults. Conversely, IL-1ra expression was significantly downregulated by LPS, H/I, or both combined, with a maximum magnitude of imbalance between IL-1 beta and sIL-1ra noticed with the double hit. The nuclear factor (NF)kappa B component of the signaling pathway activated by IL-1 beta-binding to its receptor was activated following exposure to LPS and/or H/I. We show for the first time that, perinatally, bacterial products, H/I, or both combined, induce downregulation in sIL-1ra expression concomitant with upregulation in IL-1 beta. The resulting pro-inflammatory orientation in the IL-1/IL-1ra balance might play a role in the initiation of perinatal brain damages. (C) 2008 Elsevier Ltd. All rights reserved.
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