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

Geoffrey R. Hill, Kenneth R. Cooke, Takanori Teshima, James M. Crawford, James C. Keith, Yani S. Brinson, David Bungard, James L.M. Ferrara

Research output: Contribution to journalArticlepeer-review

Abstract

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). Surprisingly, IL-11 administration polarized the donor T cell cytokine responses to host antigen after BMT with a 50% reduction in IFNγ and IL-2 secretion and a 10-fold increase in IL-4. This polarization of T cell responses was associated with reduced IFNγ 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 TNFα serum levels and suppressed TNFα 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 TNFα. We conclude that brief treatment with IL-11 may represent a novel strategy to prevent T cell-mediated inflammatory processes such as GVHD.

Original languageEnglish (US)
Pages (from-to)115-123
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number1
DOIs
StatePublished - Jul 1 1998
Externally publishedYes

Keywords

  • Endotoxin
  • Gastrointestinal tract
  • Inflammatory cytokines
  • T cells
  • Total body irradiation

ASJC Scopus subject areas

  • Medicine(all)

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