Influenza virus-induced glucocorticoid and hypothalamic and lung cytokine mRNA responses in dwarf lit/lit mice.
Influenza virus infection up-regulates cytokines such as interleukin-1beta (IL-1beta) and activates the somatotropic axis and the hypothalamic-pituitary axis. Mice with deficits in growth hormone releasing hormone (GHRH) signaling (lit/lit mice) respond to influenza virus challenge with a progressive decrease in sleep and lower survival rates. Current experiments characterize plasma glucocorticoid responses and hypothalamic and lung mRNA expression of sleep-related genes in lit/lit mice and their heterozygous controls after influenza virus challenge. lit/lit mice had higher basal and post-infection plasma corticosterone levels compared to controls. In contrast, the heterozygous mice increased hypothalamic GHRH-receptor, CRH-type 2 receptor, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) mRNAs after virus treatment while the lit/lit mice failed to up-regulate these substances. In contrast, lung levels of IL-1beta and TNF-alpha mRNAs were greater in the lit/lit mice. These data are consistent with the hypothesis that the sleep response to influenza infection is mediated, in part, by an up-regulation of hypothalamic sleep-related transcripts and they also show that a primary deficit in GHRH signaling is associated with enhanced corticosterone secretion and attenuated hypothalamic cytokine response to infection.
Alt
Jeremiah A
JA
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.
Bohnet
Stewart
S
Taishi
Ping
P
Duricka
Deborah
D
Obal
Ferenc
F
Traynor
Tim
T
Majde
Jeannine A
JA
Krueger
James M
JM
D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000276:immunology; D003345:Corticosterone / Q000097:blood* / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D013007:Growth Hormone-Releasing Hormone / Q000172:deficiency; D007031:Hypothalamus / Q000276:immunology* / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D018013:Receptors, Neuropeptide / Q000502:physiology*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000502:physiology*; D012890:Sleep / Q000276:immunology; D012893:Sleep Wake Disorders / Q000209:etiology / Q000503:physiopathology; D015854:Up-Regulation
D016207:Cytokines; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor; D003345:Corticosterone