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Cited by 153Stress Responses and CortisolAdrenal Hormones and DisordersCytomegalovirus and herpesvirus research

Endogenous glucocorticoids protect against cytokine-mediated lethality during viral infection

Ruzek, Melanie C, Pearce, Bradley D, Miller, Andrew H, Biron, Christine A·1999·The Journal of Immunology
DOI 10.4049/jimmunol.162.6.3527
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Abstract

Certain cytokines activate the hypothalamic-pituitary-adrenal axis for glucocorticoid release, and these hormones can protect against cytokine-mediated pathologies. However, endogenous activation of such a pathway has not been established during infections. A prominent glucocorticoid response peaks 36 h following murine CMV (MCMV) infection, coincident with circulating levels of the cytokines IL-12, IFN-γ, TNF, and IL-6, and dependent on IL-6 for maximal release. These studies examined functions of the hormone induction. Mice rendered glucocorticoid deficient by adrenalectomy were more susceptible than intact mice to MCMV-induced lethality, and the increased sensitivity was reversed by hormone replacement. Lack of endogenous glucocorticoids resulted in increases in IL-12, IFN-γ, TNF, and IL-6 production, as well as in mRNA expression for a wider range of cytokines, also including IL-1α and IL-1β. Viral burdens did not increase, and actually decreased, in the livers of glucocorticoid-deficient mice. TNF, but not IFN-γ, was required for increased lethality in the absence of endogenous hormone. These results conclusively demonstrate the importance of induced endogenous glucocorticoids in protection against life-threatening effects resulting from infection-elicited cytokine responses. Taken together with the dependence on induced IL-6, they document existence of an immune system-hypothalamic-pituitary-adrenal axis pathway for regulating endogenous responses to viral infections.

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Crossref · 10.4049/jimmunol.162.6.3527

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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 [27]

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Authors
Ruzek, M. C., Pearce, B. D., Miller, A. H., & Biron, C. A.
Affiliations
  • Brown University (US)
  • Emory University (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
1999-03
Volume
162
Issue
6
Pages
3527-3533
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.162.6.3527
OpenAlex
W1485545593
Cited by
153
References
28
Citations by year
2025: 2 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 3 · 2012: 3
FWCI
4.30
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (K02MH000680, R01-MH47674, KO2-MH00680, R01MH047674)
  • National Institute of Environmental Health Sciences (T32-ES-07272, T32ES007272)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Keywords
endogenous glucocorticoids, hypothalamic-pituitary-adrenal axis, adrenalectomy, glucocorticoid deficiency, interleukin-6, TNF-α, interferon-gamma, IL-12, interleukin-1, viral pathogenesis, cytokine gene expression, glucocorticoid replacement therapy
MeSH terms
Administration, Oral, Adrenalectomy, Animals, Corticosterone, Glucocorticoids, Herpesviridae Infections, Male, Mice, Inbred C57BL, Survival Analysis, Cytokines, Muromegalovirus, Mice, Knockout, Mice

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