Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation.

G R Hill; K R Cooke; T Teshima; J M Crawford; J C Keith; Y S Brinson; D Bungard; J L Ferrara

doi:10.1172/JCI3132

Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

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Published in Volume 102, Issue 1 on July 1, 1998
J Clin Invest. 1998;102(1):115–123. https://doi.org/10.1172/JCI3132.
© 1998 The American Society for Clinical Investigation

Published July 1, 1998 - Version history

Administration of IL-11 prevented lethal graft-versus-host disease (GVHD) in a murine bone marrow transplant (BMT) model (B6 --> B6D2F1) across MHC and minor H antigen barriers (survival at day 50: 90 vs 20%, P < 0.001). Surpisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFNgamma and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFNgamma serum levels and decreased IL-12 production in mixed lymphocyte cultures (MLC). In addition, IL-11 prevented small bowel damage and reduced serum endotoxin levels by 80%. Treatment with IL-11 also reduced TNFalpha serum levels and suppressed TNFalpha secretion by macrophages to LPS stimulation in vitro. IL-11 thus decreased GVHD morbidity and mortality by three mechanisms: (a) polarization of donor T cells; (b) protection of the small bowel; and (c) suppression of inflammatory cytokines such as TNFalpha. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.

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Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation.

G R Hill, K R Cooke, T Teshima, J M Crawford, J C Keith Jr, Y S Brinson, D Bungard, and J L Ferrara

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Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation.

G R Hill, K R Cooke, T Teshima, J M Crawford, J C Keith Jr, Y S Brinson, D Bungard, and J L Ferrara

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