title: Peripheral blood mononuclear cell proliferation and cytokine production in sheep as affected by cortisol level and duration of stress.
abstract: A large number of studies recognize glucocorticoids (Gc) as suppressors of inflammation; Gc exert an important role in coordinating the magnitude and duration of host immune responses. In the present in vitro investigation, we tested incremental levels of cortisol to verify the immunosuppressive or immunopermissive role of cortisol in sheep peripheral blood mononuclear cells (PBMC) after acute and chronic stress. Phytohemagglutinin (PHA)-stimulated PBMC were cultured for 24h and 96h at 37°C with 5% of CO2and varying cortisol levels: 10 ng/mL (baseline), 100 ng/mL (physiological poststressor), and 1,000 ng/mL [hyperactivated hypothalamic-pituitary-adrenal (HPA) axis]. The cell-free supernatants were collected for determination of IL-6, IL-1β, and IL-10 by ELISA, and the bromodeoxyuridine assay was performed on cells. Physiological cortisol concentration negatively affected the levels of IL-6 secreted by PBMC, resulting in increased cell proliferation after acute stress (24h of incubation). However, physiological cortisol concentration exhibited a reduction in cell proliferation induced by increased levels of IL-6 secreted by PBMC during chronic stress (96h of incubation). The cortisol concentration representing a hyperactivated HPA axis led to a reduction in cell proliferation after acute stress, which was probably induced by the elevated IL-10 production. Our results demonstrate that in sheep the effect of Gc on the immune system was related to the magnitude and the duration of stress. In particular, cortisol levels higher than physiological concentrations suppressed cell proliferation soon after acute stress. Instead, the physiological poststressor concentration of cortisol affected the immune responses in a bidirectional manner depending on the duration of the stressor.
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Ciliberti
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Albenzio
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Inghese
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santillo
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Marino
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sevi
authors.affiliation: Department of the Sciences of Agriculture, Food and Environment (SAFE), University of Foggia, Via Napoli, 25, 71122 Foggia, Italy. Electronic address: mariangela.caroprese@unifg.it.
authors.forename: M
authors.initials: M
authors.lastname: Caroprese
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D006854:Hydrocortisone / Q000097:blood*; D007026:Hypothalamic Area, Lateral / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000378:metabolism; D012756:Sheep; D013312:Stress, Physiological
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D010835:Phytohemagglutinins; D016753:Interleukin-10; D006854:Hydrocortisone
keywords: cortisol level; immune responses; sheep; stress