Hypothalamic-pituitary-adrenal activation by the bacterial superantigen staphylococcal enterotoxin B: Role of macrophages and T cells

Galina Shurin, Nola Shanks, Lars Nelson, Gloria Hoffman, Leaf Huang, Alexander W. Kusnecov

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen which stimulates T cells bearing the Vβ8 motif on the T-cell receptor. This stimulation is MHC class II dependent, and in vivo results in a rapid and pronounced T-cell cytokine response. Based on previous evidence that SEB stimulates corticosterone production in BALB/c mice, which possess a high percentage of Vβ8+ T cells, we explored the effects of SEB on the hypothalamic-pituitary-adrenal (HPA) axis and identified the peripheral immunologic cellular requirements for these effects. Administration of SEB stimulates corticosterone in a dose-dependent manner, with peak production of corticosterone occurring by 2 h after intraperitoneal challenge with 50 μg SEB. Challenge with staphylococcal enterotoxin A, which activates Vβ3+ and Vβ11+ T cells (deleted during ontogenesis in BALB/c mice), did not increase ACTH or corticosterone production. Furthermore, SEB challenge increased plasma ACTH, which accounted for the increased plasma corticosterone, and increased the expression of c-fos in the PVN region of the hypothalamus. In vivo elimination of macrophages did not prevent the corticosterone response to SEB, suggesting that pituitary-adrenal activation does not require macrophages. However, when mice were pretreated with the T-cell immunosuppressant cyclosporin A, the significantly increased ACTH and corticosterone production in response to SEB was dramatically attenuated. These results demonstrate that bacterial superantigens can stimulate the HPA axis, and that functional T cells may play an obligatory role in this effect.

Original languageEnglish (US)
Pages (from-to)18-28
Number of pages11
JournalNeuroendocrinology
Volume65
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Endocrine and Autonomic Systems
  • Endocrinology
  • Cellular and Molecular Neuroscience
  • Endocrinology, Diabetes and Metabolism

Keywords

  • Adrenal steroids
  • C-fos
  • Corticotropin
  • Cytokines
  • Lipopolysaccharide
  • Lymphocytes
  • Neuroimmune interactions

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