Therapeutic benefit of bortezomib on acute graft-versus-host disease is tissue specific and is associated with interleukin-6 levels

Chien Chun Steven Pai, Hui Hua Hsiao, Kai Sun, Mingyi Chen, Takeshi Hagino, Joseph Tellez, Christine Mall, Bruce R. Blazar, Arta Monjazeb, Mehrdad Abedi, William J. Murphy

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Bortezomib, a proteasome inhibitor capable of direct antitumor effects, has been shown to prevent acute graft-versus-host disease (GVHD) when administered in a short course immediately after bone marrow transplantation (BMT) in mice. However, when bortezomib is given continuously, CD4+ Tcell-mediated gastrointestinal tract damage increases GVHD mortality. To investigate the protective effects of bortezomib on other organs, we used a CD8-dependent acute GVHD (aGVHD) model of C3H.SW donor Tcells engrafted into irradiated C57BL/6 recipients (minor MHC mismatch), which lack significant gut GVHD. Our data in this model show that bortezomib can be given continuously to prevent and treat aGVHD mediated by CD8+ Tcells, but this effect is organ specific, such that only skin, and not liver, protection was observed. Despite the lack of hepatic protection, bortezomib still significantly improved survival, primarily because of its skin protection. Reduced skin GVHD by bortezomib was correlated with reduced serum and skin IL-6 levels. Administration of a blocking IL-6 antibody in this model also resulted in similar cutaneous GVHD protection. These results indicate that bortezomib or blockade of IL-6 may prevent CD8+ Tcell-mediated cutaneous acute GVHD.

Original languageEnglish (US)
Pages (from-to)1899-1904
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume20
Issue number12
DOIs
Publication statusPublished - Jan 1 2014

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Keywords

  • Anti-IL-6 therapy
  • Bortezomib
  • Skin acute graft-versus-host disease

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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