HYPOTHALAMIC-PITUITARY-ADRENAL ACTIVATION BY THE BACTERIAL SUPERANTIGEN STAPHYLOCOCCAL-ENTEROTOXIN-B - ROLE OF MACROPHAGES AND T-CELLS

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen which s timulates T cells bearing the V beta 8 motif on the T-cell receptor. T his stimulation is MHC class II dependent, and in vivo results in a ra pid and pronounced T-cell cytokine response. Based on previous evidenc e that SEB stimulates corticosterone production in BALB/c mice, which possess a high percentage of V beta 8+ T cells, we explored the effect s of SEE on the hypothalamic-pituitary-adrenal (HPA) axis and identifi ed the peripheral immunologic cellular requirements for these effects. Administration of SEB stimulates corticosterone in a dose-dependent m anner, with peak production of corticosterone occurring by 2 h after i ntraperitoneal challenge with 50 mu g SEB. Challenge with staphylococc al enterotoxin A, which activates V beta 3+ and V beta 11+ T cells (de leted during ontogenesis in BALB/c mice), did not increase ACTH or cor ticosterone production. Furthermore, SEB challenge increased plasma AC TH, which accounted for the increased plasma corticosterone, and incre ased the expression of c-fos in the PVN region of the hypothalamus. In vivo elimination of macrophages did not prevent the corticosterone re sponse to SEB, suggesting that pituitary-adrenal activation does not r equire 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 attenua ted. These results demonstrate that bacterial superantigens can stimul ate the HPA axis, and that functional T cells may play an obligatory r ole in this effect.