Value of Pretransplantation Cytokine Profiles for Predicting Acute Rejection in Renal Transplant Recipients M. Lessan-Pezeshki, A. Amirzargar, A. Fathi, M.R. Khatami, B. Einollahi, V. Pourfarziani, J. Azmandian, F. Khosravi, B. Ansaripour, and B. Nikbin ABSTRACT Episodes of acute rejection may represent an important risk factor for the development of chronic allograft nephropathy. Various studies have shown that pretransplant cytokine profiles in recipient blood are associated with transplant outcome. Serum samples were collected 24 hours before transplantation from 57 patients (38 men and 19 women of age 36  5 years) receiving kidneys from unrelated living donors. Additional samples were collected at 1 and 2 weeks after transplantation, as well as during every rejection episode. The immunosuppression consisted of a cyclosporine, prednisolone, and mycophenolate mofetil. Among the transplanted patients, 19 (33.3%) individuals experienced an acute rejection episode based on an increased level of serum creatinine and blood urea nitrogen during the first 14 days after transplantation. TGF-, IL-2 and IFN- serum levels were determined by an ELISA method using Bindermed system kits. The mean concentration of TGF- before transplantation tended to be lower among patients with acute rejection episodes compared to those with stable graft (75,265 versus 85,394 pg/mL; P = .34) and at 1 week after transplantation (77,558 versus 84,390 pg/mL), although the differences were not significant. Among patients with rejection the mean IL-2 concentration was significantly higher before, at 1 week, and at 2 weeks after transplan- tation (15.0 versus 6.8 pg/mL, P = .005; 19.0 versus 4.9 pg/mL, P = .001; and 21.1 versus 4.7 pg/mL, P = .0001). The mean concentration of IFN- was significantly higher pre- and at 1 and 2 weeks posttransplantation in patients with acute rejection episodes (161.1 versus 65.2, 175.6 versus 66.5 and 173.7 versus 77.1 pg/mL, all P  .001). In conclusion, evaluation of Th1 cytokines before transplantation may represent valuable predictive marker for an acute rejection episode. C YTOKINES PLAYa central role in directing both the magnitude and type of immune response generated against organ transplants. These substances, which are normally expressed at low levels, are rapidly upregulated at the onset of an immune response. Consequently, they are early predictors of graft dysfunction, and, in theory, might provide information about mechanisms that underlie im- mune attacks. 1 Acute rejection episodes (ARE) are a major cause of morbidity in renal transplant recipients, and may be considered an important factor in the development of chronic allograft nephropathy. 2 The T-helper (Th1) cytokines—Interleukin (IL)-2 and interferon gamma (IFN-)—promote the cellular immune response, specifically activating cytotoxic T lymphocytes, natural killer cells, and monocytes. These effector cells infiltrate the graft causing cellular rejection. 3 Transforming growth factor- (TGF-), a pleiotropic, multifunctional cytokine, is transported to the circulation after being pro- duced by a wide variety of cells, including monocytes, lymphocytes, renal tubular cells, endothelial cells, and airway epithelial cells. TGF- is a fibrogenic cytokine that may be an important mediator of chronic rejection in renal transplants. 4 Nicholson et al 5 reported a correlation be- tween increased TGF- mRNA and increased mRNA for collagens as well as tissue inhibitors of metalloproteinases From the Imam Khomeini Medical Center, Tehran, Iran. Address reprint requests to Mahboob Lessan-Pezeshki, Ne- phrology Department, Keshavarz Blvd., Tehran, Iran. E-mail: lessanpezeshki@yahoo.com 0041-1345/05/$–see front matter © 2005 by Elsevier Inc. All rights reserved. doi:10.1016/j.transproceed.2005.08.031 360 Park Avenue South, New York, NY 10010-1710 2982 Transplantation Proceedings, 37, 2982–2984 (2005)