title: Effect of tumor necrosis factor alpha and infliximab on apoptosis of B lymphocytes infected or not with Epstein-Barr virus.
abstract: Chronic inflammation and immunosuppressive therapies increase the risk of non-Hodgkin's lymphoma associated or not with Epstein-Barr virus (EBV) infection. A possible link between infliximab treatment and increased risk of lymphoma has been suggested. Indeed, infliximab induces apoptosis of monocytes and activated T lymphocytes, but its effect on B lymphocytes infected or not with EBV is unknown. Secreted tumor necrosis factor (TNF) alpha and the expression level of TNF receptor 1 (TNFR1) and TNFR2 were compared in EBV-positive and negative B-cell lines. The impact of TNFalpha and infliximab on apoptosis of EBV-positive cells was analyzed regarding the activity of NF-kappaB. Increased expression of TNFalpha in EBV-positive cells suggested that infliximab could affect their survival. However, TNFalpha or infliximab incubation had no effect on apoptosis of EBV-positive cells. Loss of NF-kappaB activity sensitized lymphoblastoid cell lines to TNFalpha-induced apoptosis, but no direct effect of infliximab on apoptosis was detected. On the basis of our in vitro data, neither TNFalpha nor infliximab has a direct effect on apoptosis of B lymphocytes and EBV-positive cell lines. Thus, if an increased incidence of lymphoma were induced by TNFalpha blockers, it would not involve a direct effect on B cells but rather an impaired immune surveillance by T cells.
authors.affiliation: INSERM E109, CHU Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris 11, 94275 Le Kremlin Bicêtre, France. fanny.baran@club-internet.fr
authors.forename: Fanny
authors.initials: F
authors.lastname: Baran-Marszak
authors.forename: Christelle
authors.initials: C
authors.lastname: Laguillier
authors.forename: Ibtissam
authors.initials: I
authors.lastname: Youlyouz
authors.forename: Jean
authors.initials: J
authors.lastname: Feuillard
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.forename: Remi
authors.initials: R
authors.lastname: Fagard
authors.forename: Martine
authors.initials: M
authors.lastname: Raphaël
mesh_terms: D000911:Antibodies, Monoclonal / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D000069285:Infliximab; D008213:Lymphocyte Activation / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab