title: Role of the hypothalamic pituitary adrenal axis and IL-6 in stress-induced reactivation of latent herpes simplex virus type 1.
abstract: 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 pituitary adrenal axis. In the present study, we tested the hypothesis that stress-induced elevation of corticosterone potentiates HSV-1 reactivation in latently infected mice. Because of the putative role of IL-6 in facilitating HSV-1 reactivation in mice, the effect of hyperthermic stress and cyanoketone treatment on IL-6 expression in the trigeminal ganglion was also measured. Preadministration of cyanoketone, a glucocorticoid synthesis inhibitor, blocked the stress-induced elevation of corticosterone in a dose-dependent manner. Furthermore, inhibition of corticosterone synthesis was correlated with reduced levels of HSV-1 reactivation in latently infected mice. Hyperthermic stress elicited a transient rise in IL-6 mRNA levels in the trigeminal ganglion, but not other cytokine transcripts investigated. In addition, there was a significant reduction in MAC-3+, CD8+, and DX5+ (NK cell marker) cells in the trigeminal ganglion of latent HSV-1-infected mice 24 h after stress. Cyanoketone blocked the stress-induced rise in IL-6 mRNA and protein expression in the trigeminal ganglion latently infected with HSV-1. Collectively, the results indicate that the activation of the hypothalamic pituitary adrenal axis plays an important role in stimulating IL-6 expression and HSV-1 reactivation in the trigeminal ganglion following hyperthermic stress of mice.
authors.affiliation: Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans 70112, USA.
authors.forename: S
authors.initials: S
authors.lastname: Noisakran
authors.forename: W P
authors.initials: WP
authors.lastname: Halford
authors.forename: L
authors.initials: L
authors.lastname: Veress
authors.forename: D J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D016827:CD8 Antigens / Q000235:genetics; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood; D003489:Cyanoketone / Q000494:pharmacology; D005260:Female; D006561:Herpes Simplex / Q000097:blood / Q000276:immunology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000276:immunology*; D006979:Hyperthermia, Induced; D007030:Hypothalamo-Hypophyseal System / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010913:Pituitary-Adrenal System / Q000276:immunology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013312:Stress, Physiological / Q000276:immunology* / Q000821:virology; D014158:Transcription, Genetic; D012668:Trigeminal Ganglion / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014775:Virus Activation / Q000187:drug effects / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D016827:CD8 Antigens; D015850:Interleukin-6; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; D003489:Cyanoketone; D003345:Corticosterone