Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues

Andrew H. Miller, Robert L. Spencer, Bradley D. Pearce, Tracy L. Pisell, Patima Tanapat, Julie J. Leung, Firdaus Dhabhar, Bruce S. McEwen, Christine A. Biron

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

During an immune challenge it has been suggested that responding cells secrete cytokines which then stimulate the release of glucocorticoids. Glucocorticoids, in turn, are believed to bind to their receptors in target immune tissues and provide feedback inhibition on evolving immune responses. The foundations for this hypothesis have been drawn primarily from studies on animal models of autoimmune and/or inflammatory processes, and the relevance of these glucocorticoid-immune interactions to viral infections has not been extensively examined. Accordingly, we infected mice with lymphocytic choriomeningitis virus (LCMV) and measured plasma corticosterone and cytosolic glucocorticoid receptor (GR) binding at multiple time points throughout the day and throughout infection (days 3, 5, 7 and 10 post infection). Despite a vigorous immune response to this virus, LCMV infection was associated with minimal and transient increases in corticosterone secretion. Interestingly, however, significant decreases in cytosolic GR were found in immune tissues. Receptor decreases were characterized by a significant decrease in GR binding during the diurnal rise in corticosterone in the spleen and thymus of infected but not uninfected animals on days 5-10 post infection. In addition, in the morning on these days, GR binding in the spleen of infected mice was decreased compared to uninfected control mice. Following an acute injection of corticosterone on day 7 post infection, LCMV-infected animals exhibited a significantly greater decrease in splenic GR binding than uninfected control mice, suggesting an increased sensitivity to corticosterone in infected animals. No changes were found in the affinity (K(d)) of the GR during infection, nor was there evidence of an infection-associated decrease in plasma corticosteroid binding globulin. The appearance of significant GR changes in the spleen and thymus, in the absence of significant elevations in corticosterone or decreases in its binding protein, suggests that cytokines and/or other factors produced within the immune tissues during infection either directly influenced GR number and/or function or influenced the local availability of corticosterone. Taken together, the results indicate that interactions between the neuroendocrine and immune systems can be modified at the level of the GR in the context of an ongoing immune response such as during a viral infection.

Original languageEnglish (US)
Pages (from-to)455-474
Number of pages20
JournalPsychoneuroendocrinology
Volume22
Issue number6
DOIs
StatePublished - Aug 1 1997
Externally publishedYes

Fingerprint

Glucocorticoid Receptors
Virus Diseases
Corticosterone
Lymphocytic choriomeningitis virus
Infection
Glucocorticoids
Spleen
Thymus Gland
Transcortin
Cytokines
corticosterone receptor
Neurosecretory Systems
Immune System
Carrier Proteins
Animal Models
Viruses
Injections

Keywords

  • Adrenal steroids
  • Corticosteriod binding globulin
  • LCMV
  • Neuroimmunology
  • Poly I:C
  • Virus

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Miller, A. H., Spencer, R. L., Pearce, B. D., Pisell, T. L., Tanapat, P., Leung, J. J., ... Biron, C. A. (1997). Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues. Psychoneuroendocrinology, 22(6), 455-474. https://doi.org/10.1016/S0306-4530(97)00028-0

Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues. / Miller, Andrew H.; Spencer, Robert L.; Pearce, Bradley D.; Pisell, Tracy L.; Tanapat, Patima; Leung, Julie J.; Dhabhar, Firdaus; McEwen, Bruce S.; Biron, Christine A.

In: Psychoneuroendocrinology, Vol. 22, No. 6, 01.08.1997, p. 455-474.

Research output: Contribution to journalArticle

Miller, AH, Spencer, RL, Pearce, BD, Pisell, TL, Tanapat, P, Leung, JJ, Dhabhar, F, McEwen, BS & Biron, CA 1997, 'Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues', Psychoneuroendocrinology, vol. 22, no. 6, pp. 455-474. https://doi.org/10.1016/S0306-4530(97)00028-0
Miller, Andrew H. ; Spencer, Robert L. ; Pearce, Bradley D. ; Pisell, Tracy L. ; Tanapat, Patima ; Leung, Julie J. ; Dhabhar, Firdaus ; McEwen, Bruce S. ; Biron, Christine A. / Effects of viral infection on corticosterone secretion and glucocorticoid receptor binding in immune tissues. In: Psychoneuroendocrinology. 1997 ; Vol. 22, No. 6. pp. 455-474.
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