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Leukocyte ACHT : a link between the neuroendocrine and immune systems
Thesis (Ph.D.(Med.Sciences) -- University of Stellenbosch, 1992.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2012
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| _version_ | 1867614026075209730 |
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| access_status_str | Open Access |
| author | Ferreira, Johan Andries |
| author2 | Taljaard, J. J. F. |
| author_browse | Ferreira, Johan Andries Taljaard, J. J. F. |
| author_facet | Taljaard, J. J. F. Ferreira, Johan Andries |
| author_sort | Ferreira, Johan Andries |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (Ph.D.(Med.Sciences) -- University of Stellenbosch, 1992. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/57809 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:45:29.584Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2012 |
| publishDateRange | 2012 |
| publishDateSort | 2012 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/57809 Leukocyte ACHT : a link between the neuroendocrine and immune systems Ferreira, Johan Andries Taljaard, J. J. F. Carstens, M. E. Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Pathology. Division of Chemical Pathology. Neuroendocrinology Immunity -- Endocrine aspects Dissertations -- Medicine Thesis (Ph.D.(Med.Sciences) -- University of Stellenbosch, 1992. Interactions between the neuroendocrine (hypothalamic-pituitary-adrenal) and the immune systems represent a well-documented biological phenomenon. These systems communicate and maintain homeostasis via various mechanisms, including the use of common signal and recognition molecules. One of the common signal molecules shared between the immune and neuroendocrine systems is adrenocorticotropin (ACTH). The present study was conducted to explore the link between these two systems, emphasising the role of leukocyte ACTH. In the first phase, basal leukocyte ACTH production was investigated. In the second phase, the role of the noradrenergic system, with special emphasis on the involvement of β-adrenoceptors, was investigated. In the third phase, the role of the glucocorticoid system on all of the above was investigated. These investigations have shown that pro-opiomelanocortin-derived molecules are being produced in vitro by cells of the immune system in a constitutive manner. A steady increase in concentration of ACTH occurs over three days in culture. Thus, unstimulated leukocytes are capable of ACTH production and both T and B lymphocytes are involved in this process. Individuals vary tremendously as far as both basal and cultured ACTH production are concerned, possibly as a result of differing levels of serum cholesterol, magnesium, zinc and noradrenaline. The involvement of free radicals in the ACTH synthesis process is also evident from this study, based on the stimulatory effect of ascorbic acid on ACTH production. The effects of β-adrenergic manipulation on ACTH production by unstimulated human leukocytes are reported in the present study for the first time. A drug, 3-isobutyl-1-methyl-xanthine, known to inhibit degradation of cAMP, the second messenger of \(\beta \)-adrenergic stimulation, was shown to stimulate ACTH production by leukocytes, suggesting a stimulatory effect of the noradrenergic system on leukocyte ACTH production. Additional evidence for noradrenergic stimulation comes from the positive correlations observed between leukocyte ACTH values from different treatment regimens including the \(\beta \)-adrenoceptor agonist, isoproterenol, and ascorbic acid indicating that, over time, both isoproterenol and ascorbic acid, either alone or in combination, increase ACTH production by human leukocytes. Results obtained with the \(\beta \)-adrenergic antagonist, propranolol, indicate that chronic \(\beta \)-blockade prevents the process of desensitization caused by isoproterenol and possibly enhances coupling of \(\beta \)-adrenoceptors to adenylate cyclase, thereby causing increased ACTH production by leukocytes.In the third phase it was shown that glucocorticoids at physiological concentrations had no effect on either basal or isoproterenol-stimulated ACTH production by unstimulated leukocytes. These results represent the first attempt to investigate possible glucocorticoid modulation of noradrenergic effects on ACTH production by unstimulated human leukocytes. A statistically significant difference between ACTH levels in the absence and presence of the \(\beta \)-antagonist, propranolol in leukocytes treated with the \(\beta \)-agonist, isoproterenol and the synthetic steroid, dexamethasone suggests a possible correcting influence of the noradrenergic system on ACTH production by unstimulated human leukocytes via the glucocorticoid system. As mentioned before, ascorbic acid, a free radical scavenger, was shown to have a positive effect on ACTH production, however, this effect no longer existed in the presence of dexamethasone. Based on these combined effects, an hypothesis was proposed for the involvement of free radicals in the control of the immune system by both the noradrenergic and the glucocorticoid systems. Doctoral 2012-08-27T11:38:40Z 2012-08-27T11:38:40Z 1992 Thesis http://hdl.handle.net/10019.1/57809 en Stellenbosch University 233 pages application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Neuroendocrinology Immunity -- Endocrine aspects Dissertations -- Medicine Ferreira, Johan Andries Leukocyte ACHT : a link between the neuroendocrine and immune systems |
| title | Leukocyte ACHT : a link between the neuroendocrine and immune systems |
| title_full | Leukocyte ACHT : a link between the neuroendocrine and immune systems |
| title_fullStr | Leukocyte ACHT : a link between the neuroendocrine and immune systems |
| title_full_unstemmed | Leukocyte ACHT : a link between the neuroendocrine and immune systems |
| title_short | Leukocyte ACHT : a link between the neuroendocrine and immune systems |
| title_sort | leukocyte acht a link between the neuroendocrine and immune systems |
| topic | Neuroendocrinology Immunity -- Endocrine aspects Dissertations -- Medicine |
| url | http://hdl.handle.net/10019.1/57809 |
| work_keys_str_mv | AT ferreirajohanandries leukocyteachtalinkbetweentheneuroendocrineandimmunesystems |