Transport study of interleukin-1 inhibitors using a human in vitro model of the blood-brain barrier - Université d'Artois Access content directly
Journal Articles Brain, Behavior & Immunity - Health Year : 2021

Transport study of interleukin-1 inhibitors using a human in vitro model of the blood-brain barrier

Lisa Leickt
Erik Nordling
Christina Kaiser
  • Function : Correspondent author
  • PersonId : 1139761

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Abstract

The proinflammatory cytokine Interleukin-1 (IL-1), with its two isoforms α and β, has important roles in multiple pathogenic processes in the central nervous system. The present study aimed to evaluate and compare the blood-to-brain distribution of anakinra (IL-1 receptor antagonist), bermekimab (IL-1α antagonist) and canakinumab (IL-1β antagonist). A human in vitro model of the blood-brain barrier derived from human umbilical cord blood stem cells was used, where isolated CD34+ cells co-cultured with bovine pericytes were matured into polarized brain-like endothelial cells. Transport rates of the three test items were evaluated after 180 ​min incubation at concentrations 50, 250 and 1250 ​nM in a transwell system. We report herein that anakinra passes the human brain-like endothelial monolayer at a 4-7-fold higher rate than the monoclonal antibodies tested. Both antibodies had similar transport rates at all concentrations. No dose-dependent effects in transport rates were observed, nor any saturation effects at supraphysiological concentrations. The larger propensity of anakinra to pass this model of the human blood-brain barrier supports existing data and confirms that anakinra can reach the brain compartment at clinically relevant concentrations. As anakinra inhibits the actions of both IL-1α and IL-1β, it blocks all effects of IL-1 downstream signaling. The results herein further add to the growing body of evidence of the potential utility of anakinra to treat neuroinflammatory disorders.
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Dates and versions

hal-03472272 , version 1 (10-12-2021)

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Attribution - NonCommercial

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Elisabet Sjöström, Maxime Culot, Lisa Leickt, Mikael Åstrand, Erik Nordling, et al.. Transport study of interleukin-1 inhibitors using a human in vitro model of the blood-brain barrier. Brain, Behavior & Immunity - Health, 2021, 16, pp.100307. ⟨10.1016/j.bbih.2021.100307⟩. ⟨hal-03472272⟩

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