Browsing by Person "Reiske, Lena"

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Stress hormone-induced immunomodulation and interplay between immune cells and bacteria in response to stress hormones in domestic pigs
(2020) Reiske, Lena; Stefanski, Volker
The two main endocrine systems involved in the regulation of stress reactions are the HPA axis, leading to the synthesis of glucocorticoids like cortisol or corticosterone, and the SAM axis, whose activation is associated with the release of the catecholamines adrenaline and noradrenaline. These stress hormones modulate the function of the immune system. Although pigs in modern husbandry systems face many stressors, the consequences of elevated plasma stress hormone levels on porcine immune cell numbers and functionality are insufficiently resolved. While some research on glucocorticoid effects has been conducted, data on many parameters are missing and catecholamines have not been studied systematically in the pig, yet. It is known that stress can negatively affect pigs’ resistance to infections like salmonellosis, but the underlying mechanisms are still subject to intense research efforts, with new perspectives arising since the discovery of interkingdom-signalling and microbial catecholamine perception. The aim of this thesis was to determine the effects of cortisol, adrenaline and noradrenaline on porcine immune cell functionality and the blood numbers of different leukocyte subsets. Furthermore, the interplay of immune cells and Salmonella Typhimurium under the influence of catecholamines was investigated. Adult male castrated pigs were surgically equipped with indwelling catheters to enable stress-free blood collection and intravenous application of hormones. In an initial experiment, the effects of in vitro stress hormone treatment on lymphocyte proliferation and the production of the proinflammatory cytokine TNFa were described. Cortisol reduced both proliferation and number of TNFa producers. Both catecholamines caused an increased lymphocyte proliferation at low concentrations whereas noradrenaline drastically decreased proliferation at high concentrations. While noradrenaline had no impact on TNFa producers, they were reduced in gd T cells and monocytes upon adrenaline addition. Overall, the effects were comparable to humans in terms of direction and dose but there were some disparities regarding adrenaline. In the second part of the project, the impact of in vivo stress hormone administration on immune cell numbers and functionality was examined by infusion for 48h. Cortisol and noradrenaline led to a decreased lymphocyte proliferation but to a variable extent and all three hormones promoted phagocytic function of innate immune cells. Cortisol caused a marked increase of neutrophil numbers while almost all other cell types declined strongly. For most cell types, noradrenaline exerted similar effects but solely after 2h whereas cortisol-induced alterations lasted the whole treatment period. Adrenaline effects were mostly reduced to CD8- T cells, which were reduced at first but increased after 24h. A sharp peak in NK cell numbers after 2h adrenaline infusion is particularly noteworthy and resembles findings from rodent and human studies. Overall, both hormone groups led to a shift from adaptive to innate immunity, underpinning the picture of a promotion of fast and unspecific defence systems to respond to threats in stressful situations. In a third study, S. Typhimurium was grown in the presence of catecholamines to determine the effects of supernatants from these cultures on porcine immune cell function. Both lymphocyte proliferation and TNFα production were hampered substantially, as opposed to the findings on catecholamine effects in the first experiment. It was demonstrated that these effects were not caused by catecholamines or their oxidation products and the formation of a so-far unknown immunosuppressive substance by catecholamine-primed bacteria was assumed. The results contribute to a better understanding of the increased susceptibility to infection in stressed animals and reveal a new dimension of cross-species communication. Finally, the results of the present thesis were discussed regarding their comparability to studies in humans and rodents and previous stress experiments in pigs. Furthermore, the effects of acute and chronic stress as well as different coping styles that are characterised by a SAM or HPA predominance on animal welfare and pig health were discussed, based on the endocrine mechanisms investigated in the present thesis. Possible implications of enhanced glucocorticoid and catecholamine levels for practical pig husbandry were given. Lastly, suggestions for future research to further elucidate the impact of stress hormones on the porcine immune system and the interplay with pathogenic bacteria were made.