title: The permissive role of glucocorticoids in neuroinflammatory priming: mechanisms and insights.
abstract: OBJECTIVE
  Glucocorticoids have been universally regarded as anti-inflammatory; however, a considerable number of studies now demonstrate that under some conditions, glucocorticoids are capable of potentiating neuroinflammatory processes (i.e. priming), a permissive function of glucocorticoids. The present review addresses recent evidence that provides insight into the mechanism(s) of glucocorticoid-induced neuroinflammatory priming.
  
  
  RESULTS
  Glucocorticoids have been found to prime inflammasomes [i.e. nucleotide-binding domain, leucine-rich repeat, pyrin domain containing proteins-3 (NLRP3)], which are intracellular multiprotein complexes that mediate proinflammatory processes. Inflammasomes are activated by products of stressed or damaged cells. Interestingly, these products (damage-associated molecular patterns) are induced by stress and mediate stress-induced neuroinflammatory priming.
  
  
  CONCLUSIONS
  In light of these findings, we propose a model of glucocorticoid-induced neuroinflammatory priming whereby stress and glucocorticoids induce cellular damage/stress in the brain, the products of which prime the NLRP3 inflammasome. Thus, glucocorticoid-induced priming of the NLRP3 inflammasome may mediate the potentiated neuroinflammatory response to a subsequent proinflammatory immune challenge. We propose that during a flight-or-flight response, available energy stores should be diverted to defensive behaviours, and it might be after the emergency is over that resources should be shifted to recuperation and host defense against infection. This is the scenario that would be promoted by elevated glucocorticoids reducing ongoing inflammation while simultaneously priming the NLRP3 inflammasome.
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, Boulder, Colorado, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Frank
authors.forename: Linda R
authors.initials: LR
authors.lastname: Watkins
authors.forename: Steven F
authors.initials: SF
authors.lastname: Maier
mesh_terms: D001921:Brain / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D005938:Glucocorticoids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D005938:Glucocorticoids; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human