Cytokine secretion and latent herpes virus reactivation with 28 days of horizontal hypokinesia.
BACKGROUND
Hypokinesia is associated with spaceflight and prolonged illnesses and may lead to secondary immune deficiency.


METHODS
The distribution of immunocytes in whole blood, mitogen-induced cytokine secretion in vitro, Epstein-Barr virus (EBV) reactivation, and plasma cortisol levels were studied in 13 healthy volunteers subjected to a horizontal bed rest (BR) regime for 28 d. Samples were collected before the study, weekly during BR, and then 3-5 d after the regime ended. Additionally, subjects were treated with hydrocortisone on the 1st and 27th d of BR to simulate the hypercortisolemia that occurs during stress.


RESULTS
The factors of 28-d BR regime accompanied by acute hypercortisolemia significantly decreased the relative and absolute number of total lymphocytes, CD3+ T-cells, T-helper subset, and monocytes, but increased the percentage of the CD8+ T-cells, and NK cells at the 4th wk compared with the baseline. A significant decrease in mitogen-activated secretion of IL-2, IFN-gamma, TNF-beta, IL-6, and IL-10 was registered at the same interval. Also, secretion of IL-2 and IFN-gamma declined at the 2nd week of the BR regime. Secretion of IL-4 was significantly higher at the 2nd and 3rd weeks compared with the baseline. A significant increase in the shedding of EBV DNA in saliva was observed as early as the 3rd wk of BR.


CONCLUSIONS
Stress factors associated with BR significantly alter immune responsiveness in vitro and in vivo. Changes in the cytokine secretion and cytokine imbalance precede latent EBV reactivation. PHA/LPS-activated cytokine secretion in whole blood can be used as a test system for predicting latent virus activation.
Uchakin
Peter N
PN
Department of Internal Medicine, Mercer University School of Medicine, 1550 College Street, Macon, GA, USA. uchakin_pn@mercer.edu
Stowe
Raymond P
RP
Paddon-Jones
Douglas
D
Tobin
Brian W
BW
Ferrando
Arny A
AA
Wolfe
Robert R
RR
D000328:Adult; D000601:Amino Acids, Essential / Q000276:immunology / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D019587:Dietary Supplements; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000276:immunology; D007103:Immobilization / Q000009:adverse effects* / Q000502:physiology*; D008875:Middle Aged; D012463:Saliva / Q000821:virology; D018561:Space Simulation / Q000009:adverse effects; D013315:Stress, Psychological / Q000276:immunology / Q000821:virology; D014775:Virus Activation / Q000276:immunology*; D017735:Virus Latency / Q000276:immunology / Q000502:physiology
D000601:Amino Acids, Essential; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006854:Hydrocortisone