Glucocorticoids worsen excitotoxin-induced expression of pro-inflammatory cytokines in hippocampal cultures.
Glucocorticoids (GCs), the adrenal steroid hormones released during stress, have well-known anti-inflammatory actions. Despite that, there is increasing evidence that GCs are not uniformly anti-inflammatory in the injured nervous system and, in fact, can be pro-inflammatory. The present report continues this theme. Primary hippocampal cultures were treated with GC concentrations approximating basal, acute (1 h) stress or chronic (24 h) stress conditions and were then exposed to the excitotoxin kainic acid (KA). KA induced expression of the pro-inflammatory cytokines IL-1 beta and TNF-alpha, and chronic high dose GC exposure excacerbated this induction. In a second study, cultures were exposed to the physiological range of GC concentrations for 24 h prior to KA treatment. Low- to mid-range GC concentrations were anti-inflammatory, decreasing expression of IL-1 beta and TNF-alpha, while the highest GC doses either failed to be anti-inflammatory or even potentiated expression further. These findings add to the growing picture of these classically anti-inflammatory hormones potentially having pro-inflammatory effects in the injured CNS.
MacPherson
Anna
A
Department of Biological Sciences, Stanford University, Gilbert Laboratory MC 5020, Stanford, CA 94305-5020, USA.
Dinkel
Klaus
K
Sapolsky
Robert
R
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D013312:Stress, Physiological / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D018690:Excitatory Amino Acid Agonists; D005938:Glucocorticoids; D018836:Inflammation Mediators; D007375:Interleukin-1; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; D007608:Kainic Acid