Tissue expression of NLRP3, IL-1ß, and IL-18 in glomerular and interstitial inflammation associated with diabetic nephropathy

Abstract

Activation of the NLRP3 inflammasome and its downstream cytokines IL-1β and IL-18 has been increasingly associated with the inflammatory mechanisms underlying diabetic nephropathy (DN), the leading cause of chronic kidney disease and end-stage renal disease worldwide. This study investigated the expression of these inflammatory mediators in renal tissue from patients with DN. Eighty renal biopsies from adult patients (≥18 years) with a histopathological diagnosis of DN and 22 control samples obtained from autopsies were analyzed. NLRP3, IL-1β, and IL-18 expression was assessed by immunohistochemistry, and semi-quantitative analysis was performed to determine the proportion of immunostained cells in the glomerular and interstitial compartments. A significant increase in immunostaining for all three mediators was observed in mesangial cells, podocytes, endothelial cells, and the interstitium of DN samples compared with controls (p < 0.05). Positive and significant correlations were found between NLRP3 and IL-1β in endothelial cells (p < 0.0001; rS = 0.4720) and in the interstitium (p = 0.0230; rS = 0.2540), as well as between NLRP3 and IL-18 in podocytes (p = 0.0055; rS = 0.3074). Moreover, interstitial expression of NLRP3 and IL-1β correlated positively with serum creatinine levels (p = 0.0015; rS = 0.3708; and p = 0.0029; rS = 0.3480, respectively), suggesting an association between inflammasome-mediated inflammation and renal dysfunction. Collectively, these findings indicate that the NLRP3/IL-1β/IL-18 axis plays a central role in glomerular and interstitial injury in DN, supporting its potential as a prognostic biomarker and a promising therapeutic target for disease modulation.