HUMAN-IMMUNOGLOBULIN PREPARATIONS SUPPRESS THE OCCURRENCE OF EPSTEIN-BARR VIRUS-ASSOCIATED LYMPHOPROLIFERATION

Suppression of Epstein-Barr virus (EBV) lymphoproliferation by three c ommercial human immunoglobulin (hu-Ig) preparations, one enriched with immunoglobulin A (hu-IgA-IgG) and the other two containing more than 97% immunoglobulin G (hu-IgG) with anti-EBV antibodies was studied. Al l three human preparations suppress EBV-induced lymphoproliferation in vitro and reduce release of interleukin (IL)-6 and IL-10 dose-depende ntly, irrespective, however, of the titer of EBV-specific antibodies p resent. This result was unexpected. Human Ig also reduces human recomb inant IL-6-induced lymphoproliferation in EBV-free cultures and augmen ts low-dose human recombinant IL-10-provoked suppression. In vivo stud ies used mice with severe combined immunodeficiency (SCID), reconstitu ted with human tonsillar mononuclear cells, and then infected with EBV from B95-8-derived supernatants. Immediate injection of hu-Ig after E BV infection, if given only once, delayed, and if given every two or f our weeks, abolished the induction of EBV-associated lymphomas. Delay of hu-Ig injection by 48 hours after infection was less effective. Hu- IgG was consistently more efficacious than hu-IgA-IgG. Under these con ditions the best survival rates were obtained with sustained hu-IgG ad ministrations every two weeks. Serum hu-IL-6 and hu-IL-10 were detecta ble only in lymphoma-bearing SCID mice. Hu-Ig treatment reduced the de tectability of both cytokines. These results suggest that hu-Ig-with a ntibodies to EBV-may exert a beneficial treatment potential for EBV-in duced lymphoproliferation in immunocompromised patients. The dependenc e of this suppressive effect of hu-Ig on specific anti-EBV antibodies in vivo remains to be resolved.