Cytokine secretion and latent herpes virus reactivation with 28 days of horizontal hypokinesia

Introduction: 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 4^th wk compared with the baseline. A significant decrease in mitogen-activated secretion of IL-2, IFN-γ, TNF-β, IL-6, and IL-10 was registered at the same interval. Also, secretion of IL-2 and IFN-γ declined at the 2^nd week of the BR regime. Secretion of IL-4 was significantly higher at the 2^nd and 3^rd 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.