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.
Swinnen
L J
LJ
Department of Medicine, Loyola University Chicago, Maywood, IL 60153.
Fisher
R I
RI
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