Role of TH1/TH2 Cytokines in Kidney Allograft Rejection

Abstract

One of the major issues in contemporary kidney transplantation is prevention of acute allograft rejection episodes (AREs). Cytokines are crucial mediators of immune reactions leading to AREs. We correlated serum Th1/Th2 cytokine concentrations with AREs. The project included 44 patients undergoing kidney transplantation. During the 3-month period following the transplantation, ARE was diagnosed in 11 patients. Serum samples collected 1 day before and 2, 7, 14, and 30 days after transplantation were tested for interleukin (IL)-2, IL-4, IL-5, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α concentrations using flow cytometry. Nonrejection (NONAR) and rejection (ARE) groups of patients did not show significant differences in baseline demographic characteristics. We observed that higher pretransplantation serum levels of IFN-γ ( P = .000003) and IL-10 ( P = .000001) were associated with AREs. Our analysis also showed slightly higher IL-4 serum levels among NONAR patients up to 7 days posttransplantation, followed by a drop in concentrations in NONAR patients. In contrast, there was a continuous increase among ARE patients. No significant differences were observed in plasma levels of IL-2, IL-5, IL-10, or TNF-α between the two groups. Higher pretransplantation levels of IFN-γ and IL-10 observed in ARE patients indicated ongoing nondetected, probably nonspecific, inflammatory processes able to intensify an immune response directed against the transplanted organ leading to its acute rejection. Higher levels of IL-4 prior to and shortly after transplantation may have protective effects on graft survival. However, a prolonged, increased production of IL-4 after transplantation can also contribute to AREs.