Dissertation (PhD)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Stress related to chronic exercise affects both the immune and endocrine systems, but there
are still many issues that are poorly understood, particularly effects of stress on the
functional capacity of immune cells. This thesis probed some of these issues using
physiological models of physical and psychological stress. Both exercise training stress and
chronic psychological stress in human subjects were shown to result in an up-regulation of
spontaneous reactivity of white blood cells in vitro, using two different assays, namely a) a
peripheral blood mononuclear cell (PBMC) culture assay measuring immune cell
responsiveness and b) a relatively new flow cytometry technique for assessing activation
status of cells by their expression of the surface marker CD69, in a lymphocyte
subpopulation-specific manner. An up-regulation of immune cell activation in the absence of
an additional stressor was associated with a decreased capacity to mount a response to a
subsequent mitogen stimulus in vitro after chronic psychological stress and acute, extreme
exercise stress. Another novel finding was that cortisol high-responders to chronic
psychological stress exhibited a higher spontaneous reactivity of both CD4+ and CD8+
lymphocytes when compared to cortisol low-responders. This result indicates that chronic
exposure to cortisol may decrease its usual inhibitory effect on spontaneous T lymphocyte
responsiveness.
After optimisation of an animal model of mild, psychological stress, we demonstrated (using
an IL-6 antibody) that IL-6 is necessary for a full-blown cortisol response to chronic,
intermittent mild stress. Results also suggest that IL-6 plays a role in regulation of its own
secretion by PBMCs in response to a stressor, by maintaining the production of IL-1β in the
face of stress. Basal serum corticosterone concentration was shown to be the main
determinant of the magnitude of mitogen-stimulated PBMC secretion of IL-6 in vitro in the
stress-free controls. However, after blocking of IL-6 in vivo, IL-1β was identified as a major
regulator of IL-6 secretion by mitogen-stimulated PBMCs in vitro, independently of the
presence or absence of stress. The implications of these novel findings are that proinflammatory
cytokines are sensitively regulated during mild stress.Mean serum cortisol concentration at rest was not a useful tool to assess chronic exercise
stress after training intervention. However, classification of athletes at baseline into two
groups according to their resting serum cortisol concentration illustrated two distinct patterns
for the responses of both cortisol and the cortisol:testosterone ratio to chronic stress.
These studies on the effects of chronic stress on parameters of the endocrine stress-axis
and the immune system led to the following main conclusions: a) chronic exposure to cortisol
results in a decreased inhibition of spontaneous immune cell activity at rest, b) this increased
spontaneous activation of immune cells at rest in the absence of a stressor, is associated
with a suppression of immune capacity to respond to a subsequent challenge, c) the latter
finding is not evident under stress-free conditions where cortisol promoted immune cell IL-6
secretion, and d) IL- 1β and IL-6 are involved in the regulation of each others’ secretion. / AFRIKAANSE OPSOMMING: Chroniese oefening-verwante stres beïnvloed beide the immuun- en endokriene sisteme,
maar daar is nog baie aspekte wat swak begryp word, veral m.b.t. die effekte van stres op
die funksionele kapasiteit van immuunselle. Hierdie tesis het sommige van dié vraagpunte
ondersoek deur gebruik te maak van fisiologiese en psigologiese stres. Beide oefening
program-verwante stres en chroniese psigologiese stres in proefpersone het ‘n op-regulering
van spontane witbloedselreaktiwiteit in vitro tot gevolg gehad, wat d.m.v twee verskillende
metodes aangetoon is, naamlik a) ‘n perifere bloed mononukluêre selkultuur (PBMS-kultuur)
bepaling van immuunsel reaktiwiteit en b) ‘n relatief nuwe vloeisitometriese tegniek vir die
assessering van aktiveringsstatus van selle, deur hul uitdrukking van die oppervlakmerker
CD69, op ‘n limfosiet subpopulasie-spesifieke wyse. ‘n Opregulering van
immuunselaktiwiteit in die afwesigheid van ‘n addisionele stressor is geassosieer met ‘n
verlaagde kapsiteit om te reageer op ‘n latere mitogeniese prikkel in vitro, na chroniese
psigologiese stres en akute, erge oefeningstres. Nog ‘n nuwe bevinding was dat kortisol
hoog-respondeerders, in reaksie op chroniese psigologiese stres, ‘n hoër spontane
reaktiwiteit van beide CD4+- and CD8+-limfosiete toon in vergelyking met kortisol laagresopndeerders.
Hierdie bevinding toon aan dat chroniese blootstelling aan kortisol die
inhiberende effek daarvan op spontane reaktiwiteit van T-limfosiete verminder.
Na optimalisering van ‘n rotmodel van gematigde, psigologiese stres, het ons gedemonstreer
(deur gebruik te maak van ‘n IL-6 teenliggaam) dat IL-6 nodig is vir ‘n volledige
kortisolreaksie op chroniese, onderbroke, gematigde stres. Die resultate dui daarop dat IL-6
‘n rol in die regulering van sy eie sekresie deur PBMSe in reaksie tot ‘n stressor speel, deur
die handhawing van produksie van IL-1β in die teenwoordigheid van stres. Basale serum
kortisolkonsentrasie is as die belangrikste beslissende faktor in die omvang van mitogeengestimuleerde
PBMS sekresie van IL-6 in vitro in die stresvrye kontroles aangedui. Na
blokkering van IL-6 in vivo, is IL-1β egter as ‘n belangrike reguleerder van IL-6 sekresie deur
mitogeen-gestimuleerde PBMSe in vitro geïdentifiseer, onafhanklik van die teenwoordigheid
of afwesigheid van stres. Die implikasie van hierdie nuwe bevindinge is dat proinflammatoriese
sitokiene tydens gematigde stres sensitief gereguleer word.Die gemiddelde serum kortisolkonsentrasie in ‘n rustende toestand was nie ‘n gepaste
instrument om chroniese oefeningstres na ‘n oefenprogram-ingreep te assesseer nie. Na
basislyn klassifikasie van atlete in twee groepe volgens hul rustende serum
kortisolkonsentrasie, is twee afsonderlike patrone vir die reaksie van beide kortisol en die
kortisol:testosteroon verhouding egter aangetoon.
Hierdie studies rakende die effekte van chroniese stres op parameters van die endokriene
stres-as en die immuunsisteem het tot die volgende vernaamste gevolgtrekkings gelei: a)
chroniese blootstelling aan kortisol het ‘n verlaagde inhibisie van spontane
immuunselaktiwiteit tydens rustende toestande tot gevolg, b) hierdie verhoogde spontane
aktivering van immuunselle tydens ‘n rustende toestand word geassosieer met ‘n
onderdrukking van immuunkapasiteit om te reageer op ‘n daaropvolgende prikkel, c)
laasgenoemde bevinding is nie sigbaar tydens stresvrye toestande, wanneer kortisol IL-6
sekresie bevorder, nie en d) IL- 1β en IL-6 is betrokke by die regulering van mekaar se
sekresie.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/16070 |
| Date | 12 1900 |
| Creators | Smith, Carine |
| Contributors | Myburgh, Kathryn H., University of Stellenbosch. Faculty of Science. Dept. of Physiological Sciences. |
| Publisher | Stellenbosch : University of Stellenbosch |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 204 leaves |
| Rights | University of Stellenbosch |
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