Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids
Open accessAbstract
Lewis rats with experimental allergic encephalomyelitis (EAE), induced either by the subcutaneous injection of guinea pig myelin basic protein (MBP) or by the adoptive transfer of MBP-primed spleen cells, suffer from a single episode of paralysis from which they recover spontaneously. Animals developing EAE were found to have greatly elevated levels of corticosterone in the blood. This endogenous increase in steroid production was accompanied by lymphopenia and depressed delayed-type hypersensitivity responses to OVA, indicating that rats with EAE are immunosuppressed in an antigen-nonspecific fashion. Adrenalectomized rats given subcutaneous implants of corticosterone to maintain basal steroid levels invariably died when EAE was induced. However, if the steroid replacement therapy was adjusted to mimic the hormone levels that were observed in intact rats developing EAE, then the disease followed a nonfatal course closely resembling that seen in the nonadrenalectomized controls. Replacement therapy that achieved serum corticosterone levels slightly higher than those found in intact rats with EAE virtually suppressed the disease completely. It is concluded that endogenous corticosterone release in rats with EAE plays an essential role in the spontaneous recovery that is observed in this condition. However, the subsequent refractory phase that is characteristic of rats that have recovered from EAE induced by active immunization with MBP is not associated with chronically elevated corticosterone levels. This finding is discussed in the light of other data that suggest that unlike the spontaneous recovery, the refractory state has an immunological basis rather than an endocrinological basis.
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A deficient or blunted HPA axis is commonly observed in autoimmune and inflammatory diseases, and disrupting the HPA axis compromises survival of normally resistant mice to septic shock.
“On the other hand, a deficient or blunted HPA axis is commonly observed in the clinic in a wide range of autoimmune and inflammatory diseases. Likewise, disrupting the HPA axis surgically (through adrenalectomy) or pharmacologically (with GR antagonists) compromises the survival of normally resistant mice to septic shock (23–27).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [25]
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- Authors
- MacPhee, I. A., Antoni, F. A., & Mason, D. W.
- Affiliations
- University of Oxford (GB)
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1989-02-01
- Volume
- 169
- Issue
- 2
- Pages
- 431-445
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2189214
- OpenAlex
- W2140298451
- Cited by
- 328
- References
- 58
- Citations by year
- 2024: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 7
- FWCI
- 14.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- experimental autoimmune encephalomyelitis, spontaneous recovery, corticosterone, adrenal corticosteroids, immunosuppression, lymphopenia, delayed-type hypersensitivity, adrenalectomy, steroid replacement therapy, myelin basic protein, adoptive transfer, refractory period, Lewis rats
- MeSH terms
- Adrenal Glands, Adrenalectomy, Animals, Corticosterone, Encephalomyelitis, Autoimmune, Experimental, Immunosuppression Therapy, Leukocyte Count, Rats, Inbred Lew, Rats
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