CYTOKINE ANALYSIS OF HUMAN RENAL-ALLOGRAFT ASPIRATION BIOPSY CULTURESSUPERNATANTS PREDICTS ACUTE REJECTION

Background. A Th1 response is said to be associated with transplant re jection and Th2 with tolerance, although this is not agreed by all. Cy tokines evaluation in peripheral blood and urine in kidney transplants produces variable results. We hypothesized that measurement of major cytokines involved in Th1/Th2 paradigm on transplant renal-infiltratin g cells could bring valuable scientific and clinical information. Meth ods. Fifty-six adult cadaver kidney transplants were subdivided into 2 1 stable patients (group A), 22 suffering acute rejection (group B), 1 0 with chronic rejection (group C) and three with CMV disease (group D ). Fine-needle aspiration biopsies were cultured and their supernatant s analysed for IL-2, IL-4, IL-10 and IFN-gamma. Results. Group A produ ced small amounts of both IL-2 and IL-10 while group B synthetized sig nificantly higher IL-2 and significantly lower IL-10 amounts than grou p A. Group B produced significantly more IL-2 than A on day 7 post-tra nsplantation, several days before rejection supervened. Group C produc ed IL-10 and very low amount of IL-2. Group D produced both IL-2 and I L-10. We did not find any IL-4, and IFN-gamma was present in a few sam ples. For IL-2, sensitivity, specificity, negative and positive predic tive values for acute rejection were 100, 87.2, 94.7 and 83.3%, respec tively. Conclusions. Cytokine analysis in fine-needle aspiration biops y cultures supernatants is a very useful immunological screening metho d for kidney transplants. IL-2 synthesis on day 7 post-transplantation reliably predicted the risk of impending acute rejection during the f irst weeks. The cytokine pattern suggests that acute rejection is asso ciated with Th1, stable patients with Th0/Th2, and chronic rejection w ith Th2 patterns.