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IL-11 separates graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation. 1999

T Teshima, and G R Hill, and L Pan, and Y S Brinson, and M R van den Brink, and K R Cooke, and J L Ferrara
Department of Internal Medicine, University of Michigan Cancer Center, Ann Arbor 48109-0942, USA.

We recently showed that IL-11 prevents lethal graft-versus-host disease (GVHD) in a murine bone marrow transplantation (BMT) model of GVHD directed against MHC and minor antigens. In this study, we have investigated whether IL-11 can maintain a graft-versus-leukemia (GVL) effect. Lethally irradiated B6D2F1 mice were transplanted with either T cell-depleted (TCD) bone marrow (BM) alone or with BM and splenic T cells from allogeneic B6 donors. Animals also received host-type P815 mastocytoma cells at the time of BMT. Recipients were injected subcutaneously with recombinant human IL-11 or control diluent twice daily, from 2 days before BMT to 7 days after BMT. TCD recipients all died from leukemia by day 23. All control- and IL-11-treated allogeneic animals effectively rejected their leukemia, but IL-11 also reduced GVHD-related mortality. Examination of the cellular mechanisms of GVL and GVHD in this system showed that IL-11 selectively inhibited CD4-mediated GVHD, while retaining both CD4- and CD8-mediated GVL. In addition, IL-11 treatment did not affect cytolytic effector functions of T cells after BMT either in vivo or in vitro. Studies with perforin-deficient donor T cells demonstrated that the GVL effect was perforin dependent. These data demonstrated that IL-11 can significantly reduce CD4-dependent GVHD without impairing cytolytic function or subsequent GVL activity of CD8(+) T cells. Brief treatment with IL-11 shortly after BMT may therefore represent a novel strategy for separating GVHD and GVL.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D007942 Leukemia, Experimental Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues. Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D003602 Cytotoxicity, Immunologic The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D005260 Female Females
D006086 Graft vs Host Disease The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION. Graft-Versus-Host Disease,Homologous Wasting Disease,Runt Disease,Graft-vs-Host Disease,Disease, Graft-Versus-Host,Disease, Graft-vs-Host,Disease, Homologous Wasting,Disease, Runt,Diseases, Graft-Versus-Host,Diseases, Graft-vs-Host,Graft Versus Host Disease,Graft-Versus-Host Diseases,Graft-vs-Host Diseases
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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