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.