Cytokines insulin-dependant diabetes

Insulin-dependent diabetes mellitus (IDDM) is an example of a metabolic disease under active consideration for inducible gene therapy strategies. In this disorder, inflammatory cytokines have been shown to activate apoptosis in pancreatic beta cells. Experimental studies indicate that expression of insulinlike growth factor-1 (IGF-1) can prevent the cytokine-mediated destruction of beta cells of the pancreas (Giannoukakis et al., 2001). Regulated expression of IGF-1 in human pancreatic islets, to preserve beta cell function, may be a useful approach in the treatment of certain types of diabetes (Demeterco and Levine, 2001). 

Models of autoimmune diabetes in nonobese diabetic mice (NOD) mice, insulin-dependent diabetes, and experimental allergic encephalyomyelitis (EAE) were also used to evaluate naked pDNA therapy. In the latter models, a predominant Thl cytokine response is thought to play a role in disease symptoms and etiology. Treatment of these mouse models with a TH2 type cytokine, such as IL-10 or IL-4, has been found to shift the immune response and lessen the severity of disease. Therefore, the efficacy of pDNA delivery of a Th2 cytokine was explored in these specific models. 

Interleukin-1, pancreatic P cells, and insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus is an autoimmune disease that causes the gradual destruction of insulin-producing pancreatic P cells. It has been postulated that the infiltration of macrophages into the pancreatic islets plays a key role in the destruction of P cells and that cytokines, especially interleukin-1, which is released locally from macrophages, may be the toxic molecule causing this destruction. 

Thl proinflammatory cytokines such as IFN-y, IL-1/3, IL-12, and TNF-a released by macrophage and T lymphocytes in the vicinity of pancreatic beta cells have been implicated in the pathogenesis of type I (insulin-dependent) diabetes mellitus. Moreover, IL-18 serum levels are increased selectively during the early, subclinical stage of type I diabetes mellitus (N5). 

Rabinovitch A, Suarez-Pinzon WL. Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. Biochem Pharmacol 1998 55(8) 1139-ll49. 

Autoimmune diseases have been reported to be more frequent in human subjects treated with several recombinant cytokines [38], For instance, increased titers or the new occurrence of autoantibodies have been observed in hepatitis C patients treated with the recombinant interferons-alpha (IFNa). Quite a few clinical case reports describe the development of organ-specific as well as systemic autoimmune diseases including systemic lupus erythematosus, insulin-dependent type I diabetes mellitus, autoimmune thrombocytopenia, autoimmune hemolytic anemia, myasthenia gravis, and autoimmune thyroiditis in patients under IFNa therapy. Although the mechanism involved is not fully elucidated, the available data support the pathogenic potential of IFNa in autoimmunity [31]. In contrast, autoimmune effects associated with IFNp therapy are thought to be of lesser concern based on the current clinical evidence [38], Thyroid autoimmunity in contrast to other autoimmune diseases is frequent in patients treated with recombinant interleukin-2 (rIL-2). Thus, among 281 previously euthyroid cancer patients treated with rIL-2, up to 41%... 

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