ROLE OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IL-6 IN STRESS-INDUCED REACTIVATION OF LATENT HERPES-SIMPLEX VIRUS TYPE-1

Hyperthermic stress induces reactivation of herpes simplex virus type 1 (HSV-1) in latently infected mice and also stimulates corticosterone release from the adrenals via activation of the hypothalamic pituitar y adrenal axis. In the present study, we tested the hypothesis that st ress-induced elevation of corticosterone potentiates HSV-1 reactivatio n in latently infected mice, Because of the putative role of IL-6 in f acilitating HSV-1 reactivation in mice, the effect of hyperthermic str ess and cyanoketone treatment on IL-6 expression in the trigeminal gan glion was also measured. Preadministration of cyanoketone, a glucocort icoid synthesis inhibitor, blocked the stress-induced elevation of cor ticosterone in a dose-dependent manner, Furthermore, inhibition of cor ticosterone synthesis was correlated with reduced levels of HSV-1 reac tivation in latently infected mice. Hyperthermic stress elicited a tra nsient rise in IL-6 mRNA levels in the trigeminal ganglion, but not ot her cytokine transcripts investigated. In addition, there was a signif icant reduction in MAC-3(+), CD8(+), and DX5(+) (Ng cell marker) cells in the trigeminal ganglion of latent HSV-1-infected mice 24 h after s tress, Cyanoketone blocked the stress-induced rise in IL-6 mRNA and pr otein expression in the trigeminal ganglion latently infected with HSV -1. Collectively, the results indicate that the activation of the hypo thalamic pituitary adrenal axis plays an important role in stimulating IL-6 expression and HSV-1 reactivation in the trigeminal ganglion fol lowing hyperthermic stress of mice.