Glucocorticoids worsen excitotoxin-induced expression of pro-inflammatory cytokines in hippocampal cultures
Abstract
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.
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There are exceptions to glucocorticoid inhibition of pro-inflammatory cytokines: pro-inflammatory effects of glucocorticoids that depend on dose and cell or tissue type.
“Yet, there are exceptions – pro-inflammatory effects of glucocorticoids that depend on dose and cell or tissue type (Dinkel et al., 2003; MacPherson et al., 2005).”
From Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators (2008) · cites this paper as MacPherson et al., 2005
Proinflammatory effects of glucocorticoids depend on dose and cell or tissue type.
“Yet, there are exceptions - proinflammatory effects of glucocorticoids that depend on dose and cell or tissue type.6,7”
From Protective and damaging effects of stress mediators: central role of the brain (2006) · cites this paper as [7]
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- Authors
- MacPherson, A., Dinkel, K., & Sapolsky, R.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Sapolsky, Robert
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 194
- Issue
- 2
- Pages
- 376-383
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2082743978
- Cited by
- 120
- References
- 39
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 17 · 2017: 7 · 2016: 2 · 2015: 7 · 2014: 11 · 2013: 5 · 2012: 6
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Adler Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- glucocorticoids, excitotoxicity, kainic acid, inflammatory cytokines, IL-1β, TNF-α, hippocampus, chronic stress, acute stress, neuroinflammation, dose-dependent effects
- MeSH terms
- Animals, Cells, Cultured, Dose-Response Relationship, Drug, Drug Synergism, Glucocorticoids, Hippocampus, Interleukin-1, Kainic Acid, Neurons, Neurotoxins, Stress, Physiological, Tumor Necrosis Factor-alpha, Up-Regulation, Cytokines, Excitatory Amino Acid Agonists, Inflammation Mediators, Rats
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