Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats.
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Inbred Lewis (LEW/N) female rats develop an arthritis in response to group A streptococcal cell wall peptidoglycan polysaccharide (SCW), which mimics human rheumatoid arthritis. Histocompatible Fischer (F344/N) rats do not develop arthritis in response to the same SCW stimulus. To evaluate this difference in inflammatory reactivity, we examined the function of the hypothalamic-pituitary-adrenal (HPA) axis and its ability to modulate the development of the inflammatory response in LEW/N and F344/N rats. We have found that, in contrast to F344/N rats, LEW/N rats had markedly impaired plasma corticotropin and corticosterone responses to SCW, recombinant human interleukin 1 alpha, the serotonin agonist quipazine, and synthetic rat/human corticotropin-releasing hormone. LEW/N rats also had smaller adrenal glands and larger thymuses. Replacement doses of dexamethasone decreased the severity of LEW/N rats' SCW-induced arthritis. Conversely, treatment of F344/N rats with the glucocorticoid receptor antagonist RU 486 or the serotonin antagonist LY53857 was associated with development of severe inflammatory disease, including arthritis, in response to SCW. These findings support the concept that susceptibility of LEW/N rats to SCW arthritis is related to defective HPA axis responsiveness to inflammatory and other stress mediators and that resistance of F344/N rats to SCW arthritis is regulated by an intact HPA axis-immune system feedback loop.
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- Authors
- Sternberg, E. M., Hill, J. M., Chrousos, G. P., Kamilaris, T., Listwak, S. J., Gold, P. W., & Wilder, R. L.
- Affiliations
- National Institute of Mental Health (US)
- ORCID
- Chrousos, G P
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1989-04
- Volume
- 86
- Issue
- 7
- Pages
- 2374-2378
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC286915
- OpenAlex
- W2015611430
- Cited by
- 723
- References
- 35
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 9 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 13 · 2012: 17
- FWCI
- 13.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- Lewis rats, F344/N rats, hypothalamic-pituitary-adrenal axis, rheumatoid arthritis model, ACTH, corticosterone, interleukin-1 alpha, quipazine, corticotropin-releasing factor, glucocorticoid receptor, RU486, serotonin, dexamethasone
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Arthritis, Arthritis, Experimental, Cell Wall, Corticosterone, Dexamethasone, Female, Humans, Hypothalamo-Hypophyseal System, Inflammation, Interleukin-1, Pituitary-Adrenal System, Polysaccharides, Bacterial, Rats, Inbred F344, Rats, Inbred Lew, Rats, Inbred Strains, Recombinant Proteins, Species Specificity, Streptococcus pyogenes, Rats
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