Chapter 2 - Cytokines in diabetic nephropathy

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Abstract

Diabetic nephropathy (DN), the most common cause of end-stage renal disease (ESRD), is increasingly considered an inflammatory process characterized by leukocyte infiltration at every stage of renal involvement. Cytokines act as pleiotropic polypeptides that regulate inflammatory and immune responses, providing important signals in the pathologic and physiologic processes. Inflammation and activation of the immune system are closely involved in the pathogenesis of diabetes and its microvascular

Cytokines and Diabetes Nephropathy: Cause or Consequence?

Cytokines are a group of small molecules (approximately 8–80 kDa) with pleiotropic actions and complex networks that regulate immune responses and related signaling pathways [13]. These molecules are relevant humoral mediators of pathologic and physiologic responses and can be classified into several classes (i.e., interleukins, interferons, tumor necrosis factors, growth factors, colony-stimulating factors, and chemokines). Cytokines may trigger different cellular responses with respect to

TNF-α

Significant attentions have been paid to the role of TNF-α in the setting of DN over the past few years. TNF-α is a pleiotropic inflammatory cytokine originally produced by monocyte/macrophage, although intrinsic renal cells, including endothelial, mesangial, glomerular, dendritic, and renal tubular cells, are also able to synthesize this cytokine [30], [31], [32], [33]. No significant correlation between serum and urinary concentrations of TNF-α was found, thus suggesting an intrarenal

Diabetic Nephropathy and Gene Polymorphisms of Cytokines

Approximately, only one-third to one-half of DM patients may develop DN [92]. Traditional metabolic and hemodynamic factors such as hypertension, poor glycemic control, and albuminuria are the main known risk factors for DN. However, these factors do not fully explain the interindividual variability in nephropathy development. It is suggested that genetic variations encoding the cytokines altering their function and/or expression may strongly affect the susceptibility to the initiation,

Diabetic Nephropathy and Therapeutic Strategies Involving Cytokines

Due to the pathogenic complexity of DN, providing diabetic patients protection from the development and progression of renal injury remains a challenge for physicians. Traditionally, DN is viewed as a result of interactions among metabolic and hemodynamic factors that activate diverse pathways leading to renal damage. Growing evidences have indicated that cytokines participate in the pathogenic process of DN; therefore, strategies modulating the cytokines may offer a new approach to the therapy

Conclusions

Developing ideal therapeutic agents that effectively blunt the development and progression of DN is an important issue for physicians. Together with traditional metabolic and hemodynamic risk factors, inflammation especially cytokines exert an important role in the pathogenic complexity of development and progression during DN process, though various cytokines contribute to DN differently. Genetic variations may also participate in the susceptibility to initiation, progression, and/or

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