Effect of tumor necrosis factor alpha and infliximab on apoptosis of B lymphocytes infected or not with Epstein-Barr virus.
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.
Baran-Marszak
Fanny
F
INSERM E109, CHU Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris 11, 94275 Le Kremlin Bicêtre, France. fanny.baran@club-internet.fr
Laguillier
Christelle
C
Youlyouz
Ibtissam
I
Feuillard
Jean
J
Mariette
Xavier
X
Fagard
Remi
R
Raphaël
Martine
M
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*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab