EXPRESSION OF CYTOKINE MESSENGER-RNA AFTER HEART-TRANSPLANTATION - RELATIONSHIP WITH REJECTION AND SERUM CYTOKINES

Different groups of cytokines may initiate or inhibit the rejection pr ocess, We used the polymerase chain reaction to study the expression o f cytokine mRNA for interleukin (IL)-2, -4, -6 and -10, tumor necrosis factor-alpha, and interferon-gamma in 187 biopsy specimens from 24 hu man cardiac transplant recipients 5-555 days after transplantation. Cy tokine levels in the serum were also measured. Cytokine mRNA was detec ted in 38.5% of biopsy specimens, IL-10 mRNA was detected more frequen tly with mild or absent rejection (11.6% in grades 0 and 1- vs. 1.4% i n grades 2 and 3, P=0.01). Up to 90 days after transplantation, IL-2 m RNA was detected more frequently with moderate rejection (13% in grade s 2 and 3 vs, 0% in grades 0 and 1, P=0.076), and IL-4 mRNA was detect ed more frequently with mild or absent rejection (16% in grades 0 and 1- vs, 0% in grades 2 and 3, P=0.061), More than 90 days after transpl antation, IL-2 mRNA was detected more frequently with mild or absent r ejection (10% in grades 0 and 1 vs, 0% in grades 2 and 3, P=0.078). Se rum IL-4 levels corresponding to biopsy specimens positive for IL-4 mR NA were higher than those corresponding to specimens negative for IL-4 mRNA (59 pg/ml vs, 32 pg/ml medians, P=0.028). Our results suggest th at IL-10 and possibly IL-4 (T helper 2 cytokines) may suppress graft r ejection, whereas IL-2 (T helper 1 cytokine) may promote cellular reje ction, In addition, cytokine profiles may change with length of time a fter transplantation. The association of elevated serum levels of IL-4 with increased expression of intragraft IL-4 mRNA may suggest release of this cytokine from the graft into the circulation.