Epstein-Barr virus-dependent lymphoproliferative disease: critical role ofIL-6

Epstein-Barr virus (EBV)-induced lymphoproliferative disease (lpd) is a B c ell neoplasm that affects patients who are immunosuppressed in the context of organ transplantation or HIV infection. A model for the aggressive form of this entity was generated by xenotransplantation of SCID mice with human peripheral blood leukocytes from individuals with prior contact with EBV. This model, where large B cell lymphoma occurs, was used to test the hypoth esis that IL-6 has a major role in EBV-induced B cell tumorigenesis. IL-6 i s known to differentiate B cells into immunoglobulin-secreting plasma cells and induce EBV replication, and xeno-chimeric animals have detectable seru m levels of human IL-6. Human IL-6 inhibition with a neutralizing monoclona l antibody decreased tumor incidence from 62 % to 27 %. In addition, anti-I L-6 treatment significantly improved xenotransplanted animal survival, with median survival at > 245 days when compared to that of controls at 132 day s. In conclusion, IL-6 plays a critical role in the pathogenesis of EBV-ind uced human lpd, and IL-6 inhibition may represent a new and promising preve ntive or therapeutic approach against this malignancy.