Tumor necrosis factor-alpha as a therapeutic target for diabetic nephropathy.
Activation of innate immunity with the subsequent development of a chronic low-grade inflammatory response is now recognized as a critical factor in the pathogenesis of diabetes mellitus and diabetic complications, including diabetic nephropathy. In the setting of diabetic nephropathy, there is now evidence of the relevant contribution of pro-inflammatory cytokines, with special participation of tumor necrosis factor-alpha (TNF-alpha). This new pathogenic perspective leads to new therapeutic implications derived from modulation of inflammation and inflammatory cytokines. Experimental studies have shown the beneficial renal actions derived from TNF-alpha inhibition with the use of soluble TNF-alpha receptor fusion proteins, chimeric monoclonal antibodies and pentoxifylline (PTF). Clinical application of this strategy is nowadays limited to PTF administration, which has demonstrated significant beneficial effects in patients with diabetic nephropathy. Overall, these studies indicate that inhibition of TNF-alpha might be an efficacious treatment for renal disease secondary to diabetes mellitus.
Navarro-González
Juan F
JF
Nephrology Service, Univeristy Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain. jnavgon@gobiernodecanarias.org
Jarque
Ana
A
Muros
Mercedes
M
Mora
Carmen
C
García
Javier
J
D000818:Animals; D016207:Cytokines / Q000502:physiology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D010431:Pentoxifylline / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline