INTERLEUKIN-8 EXPRESSION IN PATIENTS AFTER RENAL-TRANSPLANTATION

Cellular invasion and cytokine release are important steps in the init iation of rejection, We studied the release of interleukin-8 (IL-8), a potent proinflammatory and chemotactic cytokine, and its prognostic s ignificance in predicting rejection after renal transplantation. Serum and urine samples were analyzed with an IL-8-specific sandwich enzyme -linked immunosorbent assay, Biopsy tissue specimens (n = 20) were sna p-frozen and examined with immunohistochemistry using two monoclonal a ntibodies against human IL-8 (4G9 and 2A8). Serum IL-8 measurements we re of no value in predicting rejection due to low sensitivity (24%), I n 45 biopsy-proven acute rejections (<2 months after transplantation), urinary IL-8 concentrations were elevated in 62% (298 +/- 54 pg/mL; P < 0.01), preceding clinical diagnosis of rejection, After treatment, the IL-8 concentration in urine decreased back to normal (33 +/- 4 pg/ mL; P < 0.01), The highest urinary IL-8 concentrations were seen in pa tients with biopsy-proven rejection in combination with acute tubular necrosis (610 +/- 150 pg/ml), This finding was independent of renal fu nction and urinary volume. Only three of 15 rejection episodes in pati ents more than 2 months after transplantation showed an elevated IL-8 concentration in urine (94 +/- 60 pg/mL), In 10 of 23 patients with in fection, a significant increase of IL-8 in urine was observed as well (157 +/- 67 pg/mL; P < 0.05). IL-8-positive staining was found within interstitial mononuclear cells of all biopsy specimens showing rejecti on. Additionally, the antibody 4G9 stained arteriolar smooth muscle an d tubular cells, Interestingly, a few IL-8-positive cells were present in two donor kidneys before transplantation was performed; control ti ssue was negative, Further investigations are necessary to determine t he clinical value of urinary IL-8 determinations in the diagnosis of r ejection and to evaluate the role of IL-8 in the pathogenesis of acute allograft rejection. (C) 1997 by the National Kidney Foundation, Inc.