IL-2-induced GVHD protection is not inhibited by cyclosporine and is maximal when IL-2 is given over a 25 h period beginning on the day following bone marrow transplantation.
We have recently demonstrated, in a fully MHC-mis-matched murine bone marrow transplantation (BMT) model, that administration of a short course of high-dose interleukin 2 (IL-2) markedly delays the onset of graft-versus-host disease (GVHD) without compromising alloengraftment or the graft-versus-leukemia (GVL) effect of allogeneic T cells. Early timing of IL-2 administration and high dose were shown to be critical to achieve this protective effect. Although a 2.5 day course of IL-2, begun on the day of BMT, was found to confer marked protection without observable toxicity, shorter courses and a higher dose of IL-2 than 5 x 10(4) Cetus units per treatment have not been previously evaluated in this model. We now demonstrate that administration of a three-treatment course of IL-2 over a 25 h period beginning 15 h following BMT is sufficient to provide maximal GVHD protection, that increasing the IL-2 dose beyond 5 x 10(4) units per treatment does not further improve the level of GVHD protection, and that further division of IL-2 treatments to achieve more constant tissue levels does not result in improved GVHD protection. We also demonstrate that IL-2 is still protective when administered in combination with cyclosporine. These results suggest that IL-2 administered in a sufficient short course to avoid toxicity might have the potential to achieve effective GVHD prophylaxis in humans, even if given in combination with cyclosporine.
Sykes
M
M
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
Pearson
D A
DA
Szot
G L
GL
D000818:Animals; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control*; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate; D014184:Transplantation, Homologous
D007376:Interleukin-2; D016572:Cyclosporine