A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis

T. Ben-Hur*, R. Cialic, A. Itzik, O. Barak, R. Yirmiya, J. Weidenfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Herpes simplex virus type 1 (HSV-1) encephalitis may present with fever and behavioral changes, to the extent of a psychotic state and psychomotor agitation. We developed a clinically relevant experimental model of HSV-1 encephalitis and investigated host brain responses associated with its clinical signs and whether these responses depend on the presence of circulating glucocorticoids. Intracerebral inoculation of HSV-1 in rats induced fever, motor hyperactivity and aggressive behavior. In adrenalectomized rats HSV-1 failed to induce these signs, although mortality rate was identical to sham-operated rats. Hypophysectomy or blocking glucocorticoid receptors also prevented HSV-1-induced fever. Dexamethasone replacement therapy to adrenalectomized rats restored the HSV-1-induced fever and behavioral abnormalities. HSV-1 inoculation produced hyperproduction of prostaglandin E2 by brain slices. This effect was abolished in adrenalectomized rats and was restored by dexamethasone treatment. In intact rats HSV-1 induced brain interleukin-1β (IL-1β) gene expression. Adrenalectomy alone caused brain IL-1β expression, which did not increase after HSV-1 infection. Similarly, HSV-1 induced IL-1β expression in astrocyte cultures. Removal of cortisol from the culture medium caused basal IL-1β mRNA expression which was not increased by infection. In conclusion, fever, motor hyperactivity and aggressive behavior during experimental HSV-1 encephalitis are dependent on brain responses, including prostaglandin E2 and IL-1β synthesis. Circulating glucocorticoids play an essential permissive role in the induction of these host brain responses.

Original languageAmerican English
Pages (from-to)119-127
Number of pages9
JournalNeuroscience
Volume108
Issue number1
DOIs
StatePublished - 5 Dec 2001

Bibliographical note

Funding Information:
This work was supported by grants from the chief scientist, Israeli ministry of health, The National Institute for Psychobiology in Israel – The Charles E. Smith Foundation (Grant 1-2000), and The American Physicians Fellowship for Medicine in Israel.

Keywords

  • Adrenocortical axis
  • Fever
  • Interleukin-1
  • Motor activity
  • Prostaglandin E2
  • Viral encephalitis

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