title: Human immunoglobulin preparations suppress the occurrence of Epstein-Barr virus-associated lymphoproliferation.
abstract: Suppression of Epstein-Barr virus (EBV) lymphoproliferation by three commercial 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. All three human preparations suppress EBV-induced lymphoproliferation in vitro and reduce release of interleukin (IL)-6 and IL-10 dose-dependently, irrespective, however, of the titer of EBV-specific antibodies present. This result was unexpected. Human Ig also reduces human recombinant IL-6-induced lymphoproliferation in EBV-free cultures and augments low-dose human recombinant IL-10-provoked suppression. In vivo studies used mice with severe combined immunodeficiency (SCID), reconstituted with human tonsillar mononuclear cells, and then infected with EBV from B95-8-derived supernatants. Immediate injection of hu-Ig after EBV infection, if given only once, delayed, and if given every two or four 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 conditions the best survival rates were obtained with sustained hu-IgG administrations every two weeks. Serum hu-IL-6 and hu-IL-10 were detectable only in lymphoma-bearing SCID mice. Hu-Ig treatment reduced the detectability of both cytokines. These results suggest that hu-Ig-with antibodies to EBV-may exert a beneficial treatment potential for EBV-induced lymphoproliferation in immunocompromised patients. The dependence of this suppressive effect of hu-Ig on specific anti-EBV antibodies in vivo remains to be resolved.
authors.affiliation: Infectious Diseases Unit, University Children's Hospital of Zürich, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Nadal
authors.forename: J
authors.initials: J
authors.lastname: Guzman
authors.forename: S
authors.initials: S
authors.lastname: Fröhlich
authors.forename: D G
authors.initials: DG
authors.lastname: Braun
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000627:therapeutic use; D006410:Hematopoiesis; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology; D004854:Herpesvirus 4, Human; D006801:Humans; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000627:therapeutic use; D007167:Immunotherapy; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008232:Lymphoproliferative Disorders / Q000382:microbiology*; D051379:Mice; D016513:Mice, SCID; D014412:Tumor Virus Infections / Q000276:immunology* / Q000473:pathology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D015850:Interleukin-6; D016753:Interleukin-10