title: 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.
abstract: 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 (DAY 110), 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 10(-6) M 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-gamma producing CD4+ and CD8+ T-cells in PMA/ionomycin activated culture; 3) significantly affect secretion of IL-2, IFN-gamma, and IL-4, but not IL-10 and soluble IL-2 receptor alpha in PHA/LPS activated PBMC culture; 4) shift Type 1 vs. Type 2 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+ T-cells, 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.
authors.affiliation: Mercer University School of Medicine, Macon, GA, USA. uchakin_pn@mercer.edu
authors.forename: Peter N
authors.initials: PN
authors.lastname: Uchakin
authors.forename: Brian W
authors.initials: BW
authors.lastname: Tobin
authors.forename: Boris V
authors.initials: BV
authors.lastname: Morukov
authors.forename: Irina V
authors.initials: IV
authors.lastname: Larina
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cubbage
mesh_terms: D000328:Adult; D000917:Antibody Formation; D001510:Bed Rest; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism*; D018475:Head-Down Tilt; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007111:Immunity, Cellular; D007378:Interleukins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D018474:Weightlessness Simulation
chemical_list: D016207:Cytokines; D007378:Interleukins; D015375:Receptors, Interleukin-2; D006854:Hydrocortisone