title: Clinical review 103: T helper type 1 and 2 cytokines mediate the onset and progression of type I (insulin-dependent) diabetes.
abstract: Type I (insulin-dependent) diabetes mellitus (IDDM) is an autoimmune disease that results from the destruction of insulin-secreting pancreatic islet beta-cells by autoreactive cells and their mediators. Although its exact cause is not completely understood, it is well established that IDDM is associated with dysregulated humoral and cellular immunity, exemplified by altered production of and response to macrophage- and T cell-derived cytokines and a shift in T helper (Th) cell differentiation in favor of a pathogenic Th1 pathway. Th1 cytokines, including interleukin-2 and interferon-gamma, induced islet beta-cell destruction directly by accelerating activation-induced cell death (apoptosis) and by up-regulating the expression of select adhesion molecules, Th1 cytokines facilitated the pancreatic homing of autoreactive leukocytes, hence enhancing beta-cell destruction. More recently, a role for Th2 cytokines in IDDM pathogenesis was described. Accordingly, local production of Th2 cytokines, in particular interleukin-10, accelerated beta-cell destruction by enhancing autoreactive cell infiltration of the pancreas (insulitis) through modulation of the release of other cytokines and by modulating the microvasculature. Whereas both Th1 and Th2 cytokines are present in peripheral T cells and in the pancreas in IDDM, the mechanism of action and the kinetics of a cell damage induced by Th1 and Th2 cytokines appeared to be distinct. Collectively, this supports the idea that IDDM is not an exclusive Th1-mediated disorder as was suggested, and that both Th1 and Th2 cells and their respective mediators participate and cooperate in inducing and sustaining pancreatic islet beta-cell destruction in IDDM.
mesh_terms: D017668:Age of Onset; D000818:Animals; D016207:Cytokines / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology