Effect of IL-18 and sIL2R on aGVHD occurrence after hematopoietic stem cell transplantation in some Iranian patients

Abstract

Background Graft-versus-host disease is one of the major complications after allogeneic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T helper cells are thought to play a pivotal role in acute graft-versus-host disease aGVHD. The ability to predict the likely occurrence of graft-versus-host-disease (GVHD) after Hematopoietic Stem cell Transplantation (HSCT) would be extremely valuable. By serially measuring serum levels of soluble IL-2 receptor (sIL-2R), IL-18 and following allogeneic HSCT we tried to define their effect on aGVHD as a complication of transplantation and determine useful markers for aGVHD predictors. Samples and methods Serum sIL-2R, IL-18, levels were measured by sandwich ELISA in 219 sera samples from 39 patients (with hematological disorders before and after allogeneic HSCT) and 28 controls. All patients received transplants from HLA-identical siblings. Results 23 (58.9%) patients developed aGVHD (I–IV) and serum levels of sIL-2R and IL-18, in sera drawn before transplantation, in patients with acute graft-versus-host disease (aGVHD +), were increased in comparison to patients without acute graft-versus-host disease (aGVHD −) and to a control group and there were no significant differences in serum levels of sIL-2R and IL-18 in aGVHD − patients and controls. Serum level of IL-18, in aGVHD + patients, was increased during days 3–24 after HSCT, and there was a significant difference according to GVHD severity. In majority of patients with acute GVHD (60%), the peak levels of IL-18 and sIL-2R were achieved on day 10 after HSCT and the rise in sIL-2R and IL-18 preceded the clinical signs of GVHD (mean day 15 after BMT). The level of IL-18 in patients with aGVHD strongly correlated with the severity of aGVHD on Day 10 after HSCT. IL-18 level (before HSCT), in patients who received Busulfan and Fludarabin which were used to treat aGVHD, was lower than in patients who received Busulfan and Cyclophosphamide. Conclusion Our data concluded that IL-18 plays an important role in the development of aGVHD and the IL-18 level might be an indicator of aGVHD, reflecting the severity of the disease. These findings suggest that IL-18 may play an important role in the pathogenesis of aGVHD and that measurement of serum IL-18 levels can be a useful indicator of aGVHD.