title: Nimodipine inhibits IL-1β release stimulated by amyloid β from microglia.
abstract: OBJECTIVE
  There is growing evidence that inflammation plays a major role in the pathogenesis of neural damage caused by deposition of amyloid β (Aβ) in the brain. Nimodipine has received attention as a drug that might improve learning and reduce cognitive deficits in Alzheimer's disease, but the mechanism of action is poorly known. In this study, we tested the hypothesis that nimodipine inhibited Aβ-stimulated IL-1β release from microglia.
  
  
  METHODS
  Cultures of N13 microglia cells or primary mouse microglia were treated with nimodipine, and intracellular accumulation and release of IL-1β in response to Aβ or to the P2 receptor agonists ATP and benzoyl ATP (BzATP) were measured. Accumulation of IL-1β was measured in vivo after intrahippocampal inoculation of Aβ in the absence or presence of nimodipine. The effect of nimodipine on Aβ-triggered cytotoxicity was also investigated.
  
  
  RESULTS
  We show here that nimodipine dose-dependently inhibited Aβ-stimulated IL-1β synthesis and release from primary microglia and microglia cell lines. Furthermore, nimodipine also inhibited Aβ-induced IL-1βin vivo accumulation at concentrations known to be reached in the CNS. Finally, nimodipine protected microglia from Aβ-dependent cytotoxicity.
  
  
  CONCLUSIONS
  These data suggest that alleviation of symptoms of Alzheimer's disease following nimodipine administration might be due to an anti-inflammatory effect and point to a novel role for nimodipine as a centrally acting anti-inflammatory drug.
authors: Department of Clinical and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors: J M
authors: JM
authors: Sanz
authors: P
authors: P
authors: Chiozzi
authors: M
authors: M
authors: Colaianna
authors: M
authors: M
authors: Zotti
authors: D
authors: D
authors: Ferrari
authors: L
authors: L
authors: Trabace
authors: G
authors: G
authors: Zuliani
authors: F
authors: F
authors: Di Virgilio
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D009553:Nimodipine