INTERLEUKIN-6 EXPRESSION AFTER RENAL-TRANSPLANTATION

Background. Interleukin-6 (IL-6) is an inflammatory cytokine that play s a role in transplant rejection. We tested the hypothesis that IL-6 l evels in serum or urine could be of value in predicting acute and chro nic allograft rejection. Furthermore, we examined whether or not such levels reflected IL-6 expression in the kidney. Methods. We measured I L-6 and IL-6 soluble receptor (IL-6sR) in serum and urine of 145 trans plant patients and 20 normal controls. In parallel, we studied 108 ren al biopsies. IL-6 was measured with a bioassay system using an IL-6 de pendent cell line. IL-6sR was measured with enzyme-linked immunosorben t assay. The biopsies were examined for IL-6 and IL-6 receptor (IL-GR) expression with immunohistochemistry. Results. Rejection episodes occ urring within 2 months of transplantation were accompanied by elevated IL-6 concentrations in serum (17 +/- 4.8 pg/ml, P<0.05) and urine (11 4 +/- 27 pg/ml, P<0.005), compared to controls. These values returned towards baseline (0-5 pg/ml) after successful rejection treatment. The sensitivity of urine measurements was much higher (93%) than serum (5 4%). The specificity in serum (70%) and urine (60%) was reduced by inf ection, acute tubular necrosis, and antithymocyte globulin treatment. Serum and urine IL-6sR values did not correlate with rejection. In bio psy tissue, IL-6 and IL-6R were both elevated during rejection. Especi ally, mononuclear cells within the interstitial infiltrate stained pos itive. However, the amount of IL-6 positive cells did not correlate wi th peripheral IL-6 concentrations. Conclusions. Urine but not serum IL -6 values are sensitive indicators of rejection; however, they are con founded by infection, acute tubular necrosis, and certain antirejectio n treatments. These features limit their usefulness.