Type 1 vs. type 2 cytokine secretion in vitro and its regulation by hydrocortisone in humans subjected to 120-day anti-orthostatic bed-rest regime.

Uchakin, P.N., B. Tobin, B. Morukov, I. Larina, and M. Cubbage. Type 1 vs. type 2 cytokine secretion in vitro and its regulation by hydrocortizone in humans subjected to 120-day anti-orthostatic bed-rest regime. J. Grav. Physiol. 9(2)71-82, 2002. – Head-Down Bed-Rest (HDBR) mimics some of the physiological stress effects of microgravity. Six healthy volunteers were subjected to bed-rest for 120 days. Blood samples were collected one month before (PRE), on day 110 of HDBR (DAY110), and on the 7th day after bed-rest regime ends (POST). Distribution of T-cell subsets, NK-, B-cells and monocytes was assessed in the whole blood. Distribution of cytokine secreting T-cells was assessed in PMA/ionomycin cell culture. Peripheral Blood Mononuclear Cells (PBMC) and whole blood cells (WB) were activated with a combination of PHA and LPS to assess cytokine secretion. In addition, PHA/LPS activated cell cultures were treated with 10M of hydrocortisone (HCS) in order to study stress-induced alterations in the cortisol-sensitivity of immunocytes. Results from HCS culture were compared to non-treated control cultures. Stress factors of HDBR affect immune responsiveness and immune-endocrine homeostatic interrelations in vitro as follow: 1) alter expression of surface receptor to IL-2 (CD25) by CD4 and CD8 T-cell subsets in PHA/LPS activated PBMC culture; 2) alter distribution of IL-2 and/or IFN-γ producing CD4 and CD8 T-cells in PMA/ionomycin activated culture; 3) significantly affect secretion of IL-2, IFN-γ, and IL-4, but not IL-10 and soluble IL-2 receptor α in PHA/LPS activated PBMC culture; 4) shift Type1 vs. Type2 cytokine balance in PHA/LPS activated culture toward to Type 1 response; 5) in vitro treatment with hydrocortisone unequally modulate expression of CD25 on CD4, and CD8 Tcells, as well as secretion of Type 1 and Type 2 cytokines in PHA/LPS activated PBMC culture during bed-rest regime; 6) assessment of immune profile depends from the cellular and humoral milieu of cell culture.