OKT3 monoclonal antibodies induce interleukin-6 and interleukin-10: a possible cause of lymphoproliferative disorders associated with transplantation.
The risk of posttransplantation lymphoproliferative disorder (PTLD) has increased with the use of new, highly potent immunosuppressive agents. Monoclonal anti-T-cell antibodies such as OKT3 have been associated with a particularly high risk of these frequently fatal Epstein-Barr virus (EBV)-related B-cell neoplasms. OKT3 is a powerful mitogen, raising the possibility that T-cell activation and cytokine release may facilitate the development of PTLD. Interleukin-6 and interleukin-10 have recently been shown to play major roles in B-cell neoplasia in general, and particularly in EBV-induced B-cell transformation and outgrowth. The development of PTLD after treatment with OKT3 might be mediated by the release of those cytokines. On the other hand, OKT3-related PTLD may simply be the result of the profound T-cell depletion induced by the drug, and the mechanisms for lymphomagenesis may be no different than those operative in PTLDs arising in other immunosuppressed patients. A clearer understanding of the relevant mechanisms will require further work with in vivo models of the disease and may have significant implications for the design of new immunosuppressive agents.
Department of Medicine, Loyola University Chicago, Maywood, IL 60153.
L J
LJ
Swinnen
R I
RI
Fisher
D000818:Animals; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000378:metabolism*; D016853:Muromonab-CD3 / Q000009:adverse effects* / Q000627:therapeutic use; D016377:Organ Transplantation / Q000502:physiology*
D015850:Interleukin-6; D016853:Muromonab-CD3; D016753:Interleukin-10