%0 Journal Article %1 Girard2008 %A Girard, Sylvie %A Kadhim, Hazim %A Larouche, Annie %A Roy, Mélanie %A Gobeil, Fernand %A Sebire, Guillaume %D 2008 %J Cytokine %K metabolism;Interleukin1ReceptorAntagonistProtein InbredLew etiology/metabolism/pathology;InflammationMediators Newborn;DiseaseModels Brain Animal;Female;Hypoxia-Ischemia Animals;Animals toxicity;Rats;Rats biosynthesis/metabolism;Interleukin-1beta biosynthesis/metabolism;Lipopolysaccharides %N 1 %P 54--62 %R 10.1016/j.cyto.2008.04.007 %T Pro-inflammatory disequilibrium of the IL-1 beta/IL-1ra ratio in an experimental model of perinatal brain damages induced by lipopolysaccharide and hypoxia-ischemia. %U http://dx.doi.org/10.1016/j.cyto.2008.04.007 %V 43 %X 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)-1beta 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-1beta mRNA and protein levels, with a maximum increase observed with combined LPS 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-1beta and sIL-1ra noticed with the double hit. The nuclear factor (NF)kappaB component of the signaling pathway activated by IL-1beta-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-1beta. The resulting pro-inflammatory orientation in the IL-1/IL-1ra balance might play a role in the initiation of perinatal brain damages.

@article{Girard2008, abstract = {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)-1beta 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-1beta mRNA and protein levels, with a maximum increase observed with combined LPS 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-1beta and sIL-1ra noticed with the double hit. The nuclear factor (NF)kappaB component of the signaling pathway activated by IL-1beta-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-1beta. The resulting pro-inflammatory orientation in the IL-1/IL-1ra balance might play a role in the initiation of perinatal brain damages.}, added-at = {2011-05-27T21:22:55.000+0200}, author = {Girard, Sylvie and Kadhim, Hazim and Larouche, Annie and Roy, Mélanie and Gobeil, Fernand and Sebire, Guillaume}, biburl = {https://www.bibsonomy.org/bibtex/2e2149a1dfebf3496661b27ff1b8f83cf/crc_chus}, doi = {10.1016/j.cyto.2008.04.007}, institution = {iversité de Sherbrooke, 3001 12eme Avenue Nord, Sherbrooke, Que., Canada.}, interhash = {null}, intrahash = {e2149a1dfebf3496661b27ff1b8f83cf}, journal = {Cytokine}, keywords = {metabolism;Interleukin1ReceptorAntagonistProtein InbredLew etiology/metabolism/pathology;InflammationMediators Newborn;DiseaseModels Brain Animal;Female;Hypoxia-Ischemia Animals;Animals toxicity;Rats;Rats biosynthesis/metabolism;Interleukin-1beta biosynthesis/metabolism;Lipopolysaccharides}, language = {eng}, month = Jul, number = 1, pages = {54--62}, pii = {S1043-4666(08)00117-8}, pmid = {18511291}, pst = {ppublish}, timestamp = {2011-05-27T21:22:55.000+0200}, title = {Pro-inflammatory disequilibrium of the IL-1 beta/IL-1ra ratio in an experimental model of perinatal brain damages induced by lipopolysaccharide and hypoxia-ischemia.}, url = {http://dx.doi.org/10.1016/j.cyto.2008.04.007}, volume = 43, year = 2008 }