DOES INCREASED URINARY INTERLEUKIN-1 RECEPTOR ANTAGONIST INTERLEUKIN-1-BETA RATIO INDICATE GOOD PROGNOSIS IN RENAL-TRANSPLANT RECIPIENTS

Background. Interleukin-l (IL-1) is produced by activated monocytes/ma crophages; highly increased amounts of IL-1 have been found in renal t issue in acute rejection of renal grafts. The endogenous inhibitor of IL-1, interleukin-l receptor antagonist (IL-1ra), is produced in many cells in response to the same stimulus as IL-1, There is some evidence that the balance between IL-1 and IL-1ra is important in the regulati on of inflammatory responses. In many inflammatory diseases in both hu mans and animals, a high concentration of endogenous IL-1ra or adminis tration of exogenous IL-1ra has been shown to relate to shorter recove ry time or to reduced mortality. Methods. We measured the urinary excr etion of IL-1ra and IL-1 beta during the first 3-6 posttransplant week s in 23 patients with acute rejection (69 24-hr urine samples) and in 17 patients with stable graft function (51 24-hr urine samples) and ex pressed the results as cytokine/creatinine ratios. Results. Within the follow-up time, patients with rejection had higher urinary IL-1 beta/ creatinine (ng/mmol) ratios (median 5.0 vs. 2.7; P<0.005), lower IL-1r a/creatinine (ng/mmol) ratios (median 18.1 vs. 34.2;.P<0.1), and conse quently lower IL-1ra/IL-1 beta ratios (median 3.6 vs. 20.3, P<0.005), compared with patients without rejection. In rejecting patients, IL-1r a/creatinine was constantly low and decreased even further during acut e rejection, whereas IL-1 beta/creatinine ratios increased from a medi an prerejection value of 3.5 (range not measurable to 9.0) to a median value of 8.1 (P<0.0005) (range 1.6 to 18.3) during rejection. Conclus ion. These results suggest that patients who produce high amounts of I L-1ra in relation to IL-1 beta are less prone to acute allograft rejec tion than patients with low IL-1ra/IL-1 beta ratios.