Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy

Abstract

The possibility that tumor necrosis factor (TNF) and interleukin-1 (IL-1) could participate in the development of diabetic nephropathy was evaluated in streptozocin (STZ)-treated diabetic rats. Diabetic rats were divided into two groups: aminoguanidine treated group (25 mg/kg body wt, daily i.p. injection; DM-AG group) and untreated group (DM group). Non-diabetic age-matched rats were also divided into two groups with the same manner and used as controls. After twelve weeks of treatment, glomerular basement membranes (GBM) were isolated from rats of each experimental group. When thioglycollate-elicited peritoneal macrophages (M phi) from normal rats were incubated with these GBM materials, GBM from DM group induced significantly greater levels of TNF and IL-1 production than did GBM from other three groups with at doses of 2.5 to 10 mg. The TNF and IL-1 production by stimulation of GBM from the DM-AG group were similar to those from each control group. Aminoguanidine treatment significantly decreased the accumulation of advanced glycation end-products (AGEs) in GBM of diabetic rats. These findings suggest that AGE-proteins may be involved in the production of TNF and IL-1 from M phi. AGE-induced cytokines may be implicated in the development of diabetic nephropathy.

Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade

“…Increased concentrations of inflammatory parameters (Creactive protein, sialic acid, fibrinogen, TNF-␣, IL-1, and IL-6) have been reported in patients with diabetes (3)(4)(5)(6)29). Recent studies have shown that levels of these substances increase as nephropathy progresses (6,30,31), with an independent rela- (37) reported that peritoneal macrophages that were incubated with glomerular basement membranes from diabetic rats produced significantly greater levels of TNF-␣ and IL-1 than did macrophages that were incubated with membranes from normal rats. These authors suggested for the first time that proinflammatory cytokines could participate in the development of DN.…”

“…Recent studies have highlighted the potential relevance of TNF-␣ in the development and progression of renal lesion in diabetes. Endothelial, mesangial, glomerular, and tubular epithelial cells are able to produce cytokines, and diverse experimental works have demonstrated that renal mRNA levels for TNF-␣ are significantly increased in diabetic rats compared with control rats (37)(38)(39)(40). From a pathogenic perspective, it is particularly relevant that the findings of experimental studies show that increased urinary as well as renal interstitial concentrations of TNF-␣ precede the rise in albuminuria (32,33).…”

Nuclear Factor-.KAPPA.B Activation in Diabetic Rat Kidney: Evidence for Involvement of P-Selectin in Diabetic Nephropathy

“…Activation in nuclei of these cells is induced by second messengers, because it is unlikely that glucose itself could interact with NF-κ B or its components. In this regard, angiotensins (Wang et al 1998;Zhang et al 1999), oxidative stress (Wolff 1993;Noh et al 2002), and various cytokines such as interleukin (IL)-1 (Hasegawa et al 1991), IL-6 (Suzuki et al 1995), transforming growth factor-β (Border and Noble 1993;Cooper 2001), tumor necrosis factor (Hasegawa et al 1991), and vascular endothelial growth factor (Grone et al 1995), all of which are known to activate NF-κ B (Guijarro and Egido 2001), can cause kidney damage. Many of these cytokines are produced by hematopoietic mononuclear cells including monocytes and macrophages, suggesting that infiltrating monocytes/macrophages in the kidney play a critical role in the development of chronic renal injury (Hofmann et al 1999).…”

Drugs for Diabetic Nephropathy- Full Review

“…Cytokine and growth factor play important role in renal disease [104] Cells that secrete cytokine-Tubular cells, endothelialcell, mesangial cell and epithelial cell secrete cytokine which act in autocrine or paracrine manner [104] Experimental model with diabetes shows increase expression of IL-1 [99,100] IL-1 expression in increased diabetic nephropathy in several studies [98,100] Increase level of renal IL-1 correlates with albuminuria and macrophage content [99,100,104] IL-1 Increases ICAM-1 ALSO ACTIVATE DOWNSTREAM NF-κB …”