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Title: The role of adrenal steroids in innate immune modulation
Author: Lascelles, David Anthony
ISNI:       0000 0001 3605 3030
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2007
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The age related decline of the immune system, known as immune senescence, is a process responsible for the increased mortality and morbidity from infection in the elderly. Evidence from the literature has suggested that the age related decline in the serum secretion ofthe adrenal steroid, deyhydroepiandrosterone (DHEA) may be linked to this decline in immune cell function. This study looked at the effects ofDHEA and a number of other steroids linked to the hypopituitary-adrenal-immune axis, including the sulphated form ofDHEA, DHEA-S, and the corticosteroid cortisol. The in vitro effects of these steroids on neutrophil cell function were examined and progress was made in elucidating the signalling pathways through which these steroids functioned in these cells. The effect of a lack ofadrenal steroids was also investigated with baseline measurements of innate immune function being taken from groups of subjects, such as Addison's disease and hypopituitary disease patients, with adrenal insufficiency. A number of effects were noted when adrenal steroids were applied to neutrophils in vitro. These included increased superoxide production (with DHEA-S) and migration (with cortisol and DHEA). The signalling of the previously documented inhibition ofneutrophil apoptosis by cortisol was also examined and found to be linked to NFKB. In the adrenal insufficiency patients, it was noted that natural killer (NK) cell function was significantly reduced suggesting a role for adrenal steroids in the maintenance ofthe function ofthese cells. In conclusion, it was determined that the adrenal steroids are necessary for the maintenance ofsome innate immune functions and the changes w.ttich occur in the serum levels ofthese steroids with age and trauma may explain some of the causes ofsenescence ofInnate immunity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available