Elevated levels of interleukin-18 and tumor necrosis factor-α in serum of patients with type 2 diabetes mellitus: Relationship with diabetic nephropathy

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach

“…TNF-α undoubtedly contributes to renal diabetic pathology- The presence (or absence) of DN was considered as the outcome. The following parameters were considered as predictor variables: age, sex, diabetes duration, systolic and diastolic BP, HbA 1c and the genotypes of 45 SNPs a This is a constant of the equation indicating the predicted log odds for the dependent variable (case/control) when all the coefficients for the different independent variables are set to zero TNF-α levels are correlated with urinary albumin excretion in patients with type 2 diabetes at an early stage of nephropathy [35,36], as well as in rodents with streptozotocin-induced diabetes [37], and TNF-α is a potent inducer of AGER expression in endothelial cells [38]. Taken together, although the telomeric part of the MHC III appears to be an interesting region in the context of DN, more detailed mapping and functional studies are warranted to clarify potential causality of the particular markers.…”

Therapeutic Potential of Angiostatin in Diabetic Nephropathy

“…In the early stage of DN, several proinflammatory factors such as MCP-1, TNF-␣, ICAM-1, and IL-18, have been found to be upregulated (21)(22)(23). MCP-1 is a major chemokine inducing monocyte migration and differentiation to macrophages, which augment ECM production and interstitial fibrosis in diabetic kidney (17,43,44).…”

“…Accumulating evidence suggests that inflammation plays a crucial role in DN (17)(18)(19)(20). Upregulated expression of proinflammatory cytokines, such as TNF-␣, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and IL-18, is closely associated with renal functional damage (21)(22)(23)(24). Knockout of ICAM-1 abolished diabetes-induced increase in urinary albumin excretion (UAE), glomerular hypertrophy, and mesangial matrix expansion, suggesting that inflammation may be partially responsible for the renal injury in diabetes (19).…”

Association of serum and urinary tumor necrosis factor-alpha (TNF-α) with albuminuria in diabetic nephropathy.

“…TNF-α may promote renal damage in diabetic nephropathy through several mechanisms; production of endothelin-1, cytotoxic effect on glomerular cells, stimulation of apoptosis, disruption of the intracellular junctions of the glomerular filtration barrier and increases its permeability resulting in the development of albuminuria [21]. Urinary TNF-α serves as a biomarker of renal inflammation and a predictor of ESRD in diabetic patients [22].…”