Effect of tumor necrosis factor alpha and infliximab on apoptosis of B lymphocytes infected or not with Epstein-Barr virus

Cytokine. 2006 Mar 21;33(6):337-45. doi: 10.1016/j.cyto.2006.03.005. Epub 2006 May 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / physiology*
  • Apoptosis / physiology*
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology*
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Herpesvirus 4, Human* / physiology
  • Humans
  • Infliximab
  • Lymphocyte Activation / physiology
  • Tumor Necrosis Factor-alpha / physiology*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab