Prior exposure to glucocorticoids sensitizes the neuroinflammatory and peripheral inflammatory responses to E. coli lipopolysaccharide.
Acute and chronic stress has been found to sensitize or prime the neuroinflammatory response to both peripheral and central immunologic challenges. Several studies suggest that stress-induced sensitization of neuroinflammatory processes may be mediated by the glucocorticoid (GC) response to stress. GCs, under some conditions, exhibit pro-inflammatory properties, however whether GCs are sufficient to prime neuroinflammatory responses has not been systematically investigated. In the present investigation, we tested whether acute administration of exogenous GCs would be sufficient to reproduce the stress-induced sensitization of neuroinflammatory responses under a number of different timing relationships between GC administration and immune challenge (lipopolysaccharide; LPS). We demonstrate here that GCs potentiate both the peripheral (liver) and central (hippocampus) pro-inflammatory response (e.g. TNFalpha, IL-1beta, IL-6) to a peripheral immune challenge (LPS) if GCs are administered prior (2 and 24h) to challenge. Prior exposure (24h) to GCs also potentiated the pro-inflammatory response of hippocampal microglia to LPS ex vivo. In contrast, when GCs are administered after (1h) a peripheral immune challenge, GCs suppress the pro-inflammatory response to LPS in both liver and hippocampus. GCs also up-regulated microglial activation markers including Toll-like Receptor 2. The present data suggest that the temporal relationship between GC treatment and immune challenge may be an important factor determining whether GCs exhibit pro- or anti-inflammatory properties.
Frank
Matthew G
MG
Department of Psychology and Center for Neuroscience, Campus Box 345, University of Colorado at Boulder, Boulder, CO, 80309-0345, USA. matt.frank@colorado.edu
Miguel
Zurine D
ZD
Watkins
Linda R
LR
Maier
Steven F
SF
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000276:immunology / Q000473:pathology; D006854:Hydrocortisone / Q000097:blood; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000187:drug effects / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D004731:Endotoxins; D005938:Glucocorticoids; D008070:Lipopolysaccharides; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C044101:endotoxin, Escherichia coli; D006854:Hydrocortisone