tailieunhanh - Báo cáo y học: " The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction."

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction. | Terrando et al. Critical Care 2010 14 R88 http content 14 3 R88 c CRITICAL CARE RESEARCH Open Access The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction Niccolò Terrando 1 2 António Rei Fidalgo1 Marcela Vizcaychipi1 Mario Cibelli1 4 Daqing Ma1 Claudia Monaco3 Marc Feldmann3 and Mervyn Maze 1 2 Abstract Introduction The impact of pro-inflammatory cytokines on neuroinflammation and cognitive function after lipopolysaccharide LPS challenge remains elusive. Herein we provide evidence that there is a temporal correlation between high-mobility group box 1 HMGB-1 microglial activation and cognitive dysfunction. Disabling the interleukin IL -1 signaling pathway is sufficient to reduce inflammation and ameliorate the disability. Methods Endotoxemia was induced in wild-type and IL-1R- - mice by intra peritoneal injection of E. Coli LPS 1 mg kg . Markers of inflammation were assessed both peripherally and centrally and correlated to behavioral outcome using trace fear conditioning. Results Increase in plasma tumor necrosis factor-a TNFa peaked at 30 minutes after LPS challenge. Up-regulation of IL-1 p IL-6 and HMGB-1 was more persistent with detectable levels up to day three. A 15-fold increase in IL-6 and a increase in IL-1P mRNA at 6 hours post intervention P respectively was found in the hippocampus. Reactive microgliosis was observed both at days one and three and was associated with elevated HMGB-1 and impaired memory retention P . Preemptive administration of IL-1 receptor antagonist IL-1 Ra significantly reduced plasma cytokines and hippocampal microgliosis and ameliorated cognitive dysfunction without affecting HMGB-1 levels. Similar results were observed in LPS-challenged mice lacking the IL-1 receptor to those seen in LPS-challenged wild type mice treated with IL-1Ra. Conclusions These data suggest that by blocking IL-1 signaling the inflammatory cascade to LPS is attenuated thereby .