Possible association of the immunosuppressive and B cell lymphoma-promoting properties of cyclosporine

Transplantation. 1990 Jan;49(1):191-4. doi: 10.1097/00007890-199001000-00042.

Abstract

Central to the immunosuppressive properties of cyclosporine is a drug imposed blockade of the interleukin-2 gene activation. As IL-6 stimulates antigen-activated T cells to release IL-2, we examined the influence of CsA on IL-6 gene expression and IL-6-supported T cell proliferation. Northern blot analysis revealed that CsA failed to abolish IL-6 gene expression in mitogen-activated peripheral blood mononuclear cells. In fact, increased IL-6 gene transcription and increased release of IL-6 bioactivity were detected using mitogen-activated PBMCs cultured with CsA doses (200-800 ng/ml) only slightly in excess of the minimal antiproliferative dose. CsA completely abrogated the IL-6-stimulated proliferative responses of macrophage-depleted T cells stimulated with polyvalent anti-CD3 monoclonal antibodies. It is interesting that CsA-treated patients evidence an increased incidence of polyclonal lymphoproliferative disorders and B cell lymphomas. As IL-6 fosters B cell activation and growth of EBV-transformed B cells, excessive CsA doses may support development of EBV-transformed B cell lymphomas via superinduction of the IL-6 gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / immunology
  • B-Lymphocytes
  • CD3 Complex
  • Cyclosporins / adverse effects*
  • Gene Amplification / drug effects
  • Humans
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • Lymphocyte Activation / drug effects*
  • Lymphoma / etiology*
  • Receptors, Antigen, T-Cell / immunology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Cyclosporins
  • Interleukin-6
  • Receptors, Antigen, T-Cell