Role of interleukin-12 in the development of acute graft-versus-host disease in bone marrow transplant patients

Abstract

Interleukin-12 (IL-12) is a crucial cytokine regulating cell-mediated immunity, and may contribute to the development of graft-versus-host disease (GVHD). We investigated serum IL-12 concentrations, interferon gamma (IFN-γ) production by peripheral blood lymphocytes (PBL) from allogeneic stem cell recipients after IL-12 plus anti-CD3 monoclonal antibody (mAb) stimulation. We also investigated IL-12 production by peripheral macrophages (Mφ) after lipopolysaccharide (LPS) stimulation from allogeneic stem cell recipients and patients receiving donor leukocyte transfusions (DLT) for treatment or prophylaxis of leukemia relapse and Epstein–Barr virus (EBV) lymphoproliferative disease (LPD). PBL from acute GVHD patients produced high IFN-γ levels after IL-12 plus anti-CD3 mAb stimulation, whereas PBL from patients without acute GVHD produced low levels of IFN-γ. However, serum IL-12 concentrations were low in both groups. Peripheral Mφ IL-12 production increased in patients who developed acute GVHD compared to patients without acute GVHD. Five patients receiving DLT for treatment or prophylaxis of leukemia relapse developed acute GVHD. IFN-γ production by PBL stimulated by IL-12 plus anti-CD3 mAb increased, while IL-12 production by peripheral Mφ stimulated by LPS was very high after the development of acute GVHD. However, serum IL-12 concentration remained low. Three patients receiving DLT for EBV-LPD did not develop acute GVHD with no increase of IFN-γ and IL-12 production. These results indicate that IL-12 may play an important role in the development of acute GVHD after allogeneic stem cell grafting or DLT, and increased IL-12 production by Mφ occurs with various stimuli, including LPS.