The diagnostic value of GM-CSF and IL-6 determinations in patients after renal transplantation.
Cytokines are released by graft-infiltrating cells during cellular rejection. We studied the release of GMCSF and IL-6 and their prognostic significance in predicting rejection. Sequential measurements were made in serum and urine samples with an IL-6 specific cell line and a GMCSF ELISA. Biopsy tissue was snap frozen and examined with immunohistochemical methods. The IL-6 values for normal controls (CTR) and stable transplant patients (PTS) were 5-10 pg/ml in serum and 0-2.5 pg/ml in urine. In 51 biopsy-proven rejections (AR), serum IL-6 values at least doubled in 15 (sensitivity 29%, specificity 87%; 19 +/- 7 vs. 7 +/- 2 pg/ml; P = ns). In urine an increase was observed in 29 of 36 AR (sensitivity 80%, specificity 75%; 92 +/- 34 vs. 5 +/- 1 pg/ml; P < 0.05). After treatment, IL-6 decreased in urine in 26/29 PTS to 7 +/- 2 pg/ml (P < 0.05). In three PTS, rejection persisted, as did their elevated IL-6 urine values. In PTS with urinary tract infections, IL-6 increased in the serum of 13/19 and in the urine of 10/12. GMCSF in serum was not influenced by rejection; however, urine values increased in 22/33 AR (sensitivity 67%, specificity 96%; 22 +/- 5 vs. 4.8 +/- 0.3 pg/ml; P < 0.05). These values decreased (5 +/- 0.3; P < 0.05) after treatment. During infection, increased urinary GMCSF levels were observed in 2/9 PTS. Further analysis revealed a better correlation between elevated cytokine levels and rejection episodes in the early posttransplant period. In kidneys with acute rejection, IL-6 was found in the interstitium of all PTS tested. CTR tissue was negative. In PTS GMCSF was found in arterioles and in infiltrate; however, control tissue also showed some staining. Cytokine labeling in tissue could not be correlated with serum or urine values. We concluded: (1) serum IL-6 and GMCSF are of no value in rejection; (2) in urine, they reflect rejection, especially in the early posttransplant period; however, infection confounds the results; (3) IL-6 staining in tissue may be helpful, but requires more study.