A study of interleukin-8 and defensins in urine and plasma of patients with pyelonephritis and glomerulonephritis.

Abstract

Interleukin-8 (IL-8) plays a crucial role in the recruitment and activation of polymorphonucleated leukocytes (PMN) in the site of inflammation. Defensins are specific cationic proteins from azurophil PMN granules which exert antimicrobial, cytotoxic and proinflammatory activities. Urine and plasma levels of IL-8 and defensins were studied using specific enzyme-linked immunosorbent assays. IL-8 was determined in 107 patients, including 45 with chronic glomerulonephritis (GN) and 62 with chronic pyelonephritis (PN). Urine and plasma levels of defensins were studied simultaneously in 29 patients with GN and 29 with PN. None of the patients examined showed any evidence of renal insufficiency. A group of 24 healthy volunteers was used as a control. Urinary IL-8 was significantly increased in all groups of patients comparing with healthy control (< 30 pg/ml). The level of IL-8 in the urine of patients with PN (477 +/- 114 pg/ml, mean +/- SEM) was significantly (P < 0.001) higher than in patients with GN (53 +/- 7 pg/ml). The concentration of defensins in urine of patients with GN was slightly increased in comparison with the normal level (21 +/- 3.5 ng/ml versus 15.7 +/- 2.8 ng/ml). Urinary defensins were significantly elevated in patients with PN (134 +/- 118 ng/ml, P < 0.001), and were significantly higher than in the GN group (P < 0.001). A close correlation was observed between IL-8 and defensin concentrations in urine (r = 0.62), and between the urinary leukocyte count and IL-8 level (r = 0.72). The highest levels of IL-8 were observed in patients with PN, associated with nephrolithiasis (14 patients, 822 +/- 219 pg/ml versus 367 +/- 72 pg/ml in patients with PN alone, P < 0.05). IL-8 and defensin levels increased in older patients with PN, but not in older patients with GN. The levels of IL-8 and defensins in urine were 6-10-fold higher in patients with PN than in patients with GN. Thus, there is a significant difference in IL-8 production between septic and aseptic chronic inflammatory processes in kidney. It is possible to speculate that the timing and progression of kidney inflammation is mediated by an IL-8 dependent mechanism at least in the case of PN.