Brunel University School of Health Sciences and Social Care PhD Theses
Abstract
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.T lymphocytes and macrophages appear to play an important role in
mediating ß-cell damage and causing Type 1 diabetes. Both activated T cells and
macrophages operate and interact through the release of soluble factors called
cytokines, which influence the type and magnitude of immune responses. It has been
suggested that cytokines such as TNF-α and IL-1α can damage the N-cell directly. In
Type 1 diabetes, cytokines are likely to have a critical role in individuals whose
immune system is unbalanced allowing the emergence of self-destructive processes.
To investigate this possibility, sensitive assays to detect a range of cytokines of
potential relevance to the immune pathogenesis of diabetes were establised. Using
these, serum levels of IL-1α, IL-1N, TNF-α and IL-6 (macrophage-derived
cytokines), IFN-γ and IL-2 (T helper 1 cytokine profile) and IL-4 and IL-10 (T
helper 2 profile) have been measured in patients with Type 1 diabetes of different
disease duration. Increased levels of TNF-α, IL-1α, IL-2 and IFN-γ were found in
recently diagnosed patients with Type 1 diabetes when compared with both disease
and metabolic control subjects and with normal controls. The presence of this profile
of cytokines implies activation of the TH1 subset of helper cells near to diagnosis of
Type 1 diabete