Interleukin‐17 in urine and serum of patients with nephritis

Abstract

Recent evidence suggests that interleukin-17 (IL-17) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and it is a promising marker of disease activity in lupus nephritis (LN).1 IL-17 induces the expression of various pro-inflammatory cytokines and chemokines, which increase the influx of various leukocyte subpopulations and thus, causes severe inflammation. These inflammatory mediators enhance the involvement of various leukocyte subpopulations, which ultimately leads to damage.2, 3 Nordin et al published interesting data about IL-17 levels in 120 patients with SLE.4 The authors showed an increase in the levels of IL-17 in the serum and urine of patients and their correlations with British Isles Lupus Assessment Group and SLE Disease Activity Index scores, which is consistent with other studies.5, 6 But IL-17 was not a sensitive or specific marker of SLE activity. In addition, there was no correlations of IL-17 levels in urine or serum with the histological classes of LN. We also studied the levels of IL-17 in the urine and serum of patients with chronic glomerulonephritis (CGN). The levels of IL-17 in serum did not significantly differ from the levels in healthy individuals and did not depend on the activity of nephritis. On the contrary, the levels of IL-17A in the urine of patients with CGN were significantly higher at 3.05 (2.98-3.1) pg/mg creatinine (Cr) than that in healthy individuals 2.93 (2.92-2.94) pg/mg Cr The urinary IL-17A levels were not correlated with proteinuria (R2 = 0.21, P = .29) and serum albumin (R2 = 0.24, P = .21). These results indicate a connection between IL-17 levels in urine and inflammation of renal tissue in CGN patients. Also, IL-17 levels in the urine were significantly higher in the CGN patients with advanced interstitial fibrosis and a renal dysfunction with glomerular filtration rate less than 60 mL/min/1.73 m2 (2.97 [2.96-2.99] pg/mg Cr vs. 2.99 [2.98-3.00] pg/mg Cr in normal renal function, P < .05) regardless of histological forms. Currently, the role of IL-17 in fibrotic accumulation has been discussed. Severe fibrosis in murine radiation-induced lung disease was more pronounced with regard to reduction in Th1 cells in the presence of increased number of Th17 cells and higher levels IL-17.7 IL-6 can induce glomerulosclerosis and interstitial fibrosis in the kidney directly or through activation of IL-17.8 Changes in the Th17/Treg ratio may contribute to the development of advanced tissue fibrosis by transforming growth factor-β signaling through the activation of mitogen-activated protein kinases.9 Therefore, future research is needed to compare IL-17 levels in the urine with activity and sclerosis scores in the renal tissue and renal outcomes in LN.