Abstract
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, thus considered an inflammatory disease. However, further studies are required to assess the renal damage caused by the action of these molecules. Therefore, the objective of this study was to analyze the expression of cytokines and chemokines in renal biopsies from patients with DN and to correlate it with interstitial inflammation and decreased renal function.MethodsForty-four native renal biopsies from patients with DN and 23 control cases were selected. In situ expression of eotaxin, MIP-1α (macrophage inflammatory protein-1α), IL-8 (interleukin-8), IL-4, IL-10, TNF-α (tumor necrosis factor-α), TNFR1 (tumor necrosis factor receptor-1), IL-1β, and IL-6 were evaluated by immunohistochemistry.ResultsThe DN group showed a significant increase in IL-6 (p < 0.0001), IL-1β (p < 0.0001), IL-4 (p < 0.0001) and eotaxin (p = 0.0012) expression, and a decrease in TNFR1 (p = 0.0107) and IL-8 (p = 0.0262) expression compared to the control group. However, there were no significant differences in IL-10 (p = 0.4951), TNF-α (p = 0.7534), and MIP-1α (p = 0.3816) expression among groups. Regarding interstitial inflammation, there was a significant increase in IL-6 in scores 0 and 1 compared to score 2 (p = 0.0035), in IL-10 in score 2 compared to score 0 (p = 0.0479), and in eotaxin in score 2 compared to scores 0 and 1 (p < 0.0001), whereas IL-8 (p = 0.0513) and MIP-1α (p = 0.1801) showed no significant differences. There was a tendency for negative correlation between eotaxin and estimated glomerular filtration rate (eGFR) (p = 0.0566).ConclusionsOur results indicated an increased in situ production of cytokines and chemokines in DN, including IL-6, IL-1β, IL-4, and eotaxin. It was observed that, possibly, eotaxin may have an important role in the progression of interstitial inflammation in DN and in eGFR decrease of these patients.
Highlights
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide
It is known that IL1β, IL-6, Tumor necrosis factor-α (TNF-α), IL-8, MIP-1α are relevant for the development of DN, as they are potentially involved in the onset of disease complications [7–9]
Regarding the expression of chemokines in different compartments, we observed a significant increase in eotaxin in glomerular (p = 0.0359, U = 322) and tubulointerstitial compartments (p = 0.0007, U = 254) and decrease in glomerular IL-8 (p = 0.0127, t = 2.563) in the DN group compared to the control group
Summary
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Inflammatory mediators have been implicated in the pathogenesis of DN, considered an inflammatory disease. Diabetic nephropathy (DN) is a chronic microvascular complication that affects about 20 to 30% of patients with type 2 diabetes mellitus (T2DM) It is considered the leading cause of end-stage renal failure requiring renal replacement therapy [1, 2], its pathogenesis has not yet been fully elucidated. Immune and inflammatory mechanisms play important role in the development and progression of DN, which is considered a chronic inflammatory disease [3, 4] Several cells, such as monocytes, macrophages, and lymphocytes, as well as chemokines and cytokines, have been implicated in this process [5, 6]. The extent of renal damage caused by immune cellderived cytokines and chemokines and the importance of such inflammatory mechanisms on the development and progression of DN requires further investigation [14, 15]
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