Elevated interleukin (IL)‐18 levels during acute graft‐versus‐host disease after allogeneic bone marrow transplantation

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Abstract
Acute graft‐versus‐host disease (aGVHD) after allogeneic bone marrow transplantation (BMT) is mediated by grafted T lymphocytes after their polarization into type 1 T cells. Interleukin (IL)‐18, a novel immunoregulatory cytokine, strongly stimulates type 1 T cells, therefore we postulated that IL‐18 may be involved in the pathogenesis of aGVHD. Using an enzyme‐linked immunosorbent assay (ELISA), we serially measured serum levels of IL‐18 in 37 patients with haematological malignancy before and after allogeneic BMT. Patients with aGVHD had high levels of IL‐18 that strongly correlated with the severity of aGVHD. We also found that they showed reduced serum levels of IL‐18 after appropriate treatment or at a state of resolution. IL‐18 levels were not affected by the pretransplant regimen, engraftment or bacterial infection. Compared with circulating interferon (IFN)‐γ or IL‐12 levels, serum levels of IL‐18 showed a more sensitive and specific correlation with the disease status of aGVHD. These findings suggest that IL‐18 may play important roles in the pathogenesis of aGVHD and that measurement of serum IL‐18 levels can be useful indicator of aGVHD.