title: A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.
abstract: In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Januszkiewicz
authors.forename: P
authors.initials: P
authors.lastname: Essén
authors.forename: M A
authors.initials: MA
authors.lastname: McNurlan
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.forename: P J
authors.initials: PJ
authors.lastname: Garlick
authors.forename: J
authors.initials: J
authors.lastname: Wernerman
mesh_terms: D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D004837:Epinephrine / Q000008:administration & dosage*; D005934:Glucagon / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D016130:Immunophenotyping; D007262:Infusions, Intravenous; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010649:Phenylalanine / Q000378:metabolism / Q000493:pharmacokinetics; D010835:Phytohemagglutinins / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
chemical_list: D010835:Phytohemagglutinins; D011506:Proteins; D010649:Phenylalanine; D005934:Glucagon; D006854:Hydrocortisone; D004837:Epinephrine