Role of cytokines in the pathogenesis of type 1 diabetes

Abstract

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 diabetes