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PMID: 2538840 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inflammatory mediator-induced hypothalamic-pituitary-adrenal axis activation is defective in streptococcal cell wall arthritis-susceptible Lewis rats.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 7 ·1989-04-00 ·Pages 2374-8

Sternberg EM, Hill JM, Chrousos GP, Kamilaris T, Listwak SJ, Gold PW, Wilder RL

Abstract

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.

MeSH Terms
Adrenocorticotropic Hormone/blood Animals Arthritis/physiopathology Arthritis, Experimental/physiopathology,prevention & control Cell Wall/immunology Corticosterone/blood Dexamethasone/therapeutic use Female Humans Hypothalamo-Hypophyseal System/physiopathology Inflammation Interleukin-1/immunology Pituitary-Adrenal System/physiopathology Polysaccharides, Bacterial/immunology Rats Rats, Inbred F344 Rats, Inbred Lew Rats, Inbred Strains Recombinant Proteins/immunology Species Specificity Streptococcus pyogenes/immunology
Chemicals
Interleukin-1 Polysaccharides, Bacterial Recombinant Proteins Dexamethasone Adrenocorticotropic Hormone Corticosterone
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Sternberg E M
Clinical Neurosciences Branch, National Institute of Mental Health, Bethesda, MD 20892.
Hill J M
Chrousos G P
Kamilaris T
Listwak S J
Gold P W
Wilder R L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.7.2374
Published
1989-04-00
Pages
2374-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC286915
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.86.7.2374 PMC Full Text View journal details
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