PLoS ONE (Jan 2014)

Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions.

  • Satoshi Nishiwaki,
  • Takayuki Nakayama,
  • Makoto Murata,
  • Tetsuya Nishida,
  • Seitaro Terakura,
  • Shigeki Saito,
  • Tomonori Kato,
  • Hiroki Mizuno,
  • Nobuhiko Imahashi,
  • Aika Seto,
  • Yukiyasu Ozawa,
  • Koichi Miyamura,
  • Masafumi Ito,
  • Kyosuke Takeshita,
  • Hidefumi Kato,
  • Shinya Toyokuni,
  • Keisuke Nagao,
  • Ryuzo Ueda,
  • Tomoki Naoe

DOI
https://doi.org/10.1371/journal.pone.0096252
Journal volume & issue
Vol. 9, no. 5
p. e96252

Abstract

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Macrophage infiltration of skin GVHD lesions correlates directly with disease severity, but the mechanisms underlying this relationship remain unclear and GVHD with many macrophages is a therapeutic challenge. Here, we characterize the macrophages involved in GVHD and report that dexamethasone palmitate (DP), a liposteroid, can ameliorate such GVHD by inhibiting macrophage functions. We found that host-derived macrophages could exacerbate GVHD in a mouse model through expression of higher levels of pro-inflammatory TNF-α and IFN-γ, and lower levels of anti-inflammatory IL-10 than resident macrophages in mice without GVHD. DP significantly decreased the viability and migration capacity of primary mouse macrophages compared to conventional dexamethasone in vitro. DP treatment on day 7 and day 14 decreased macrophage number, and attenuated GVHD score and subsequent mortality in a murine model. This is the first study to provide evidence that therapy for GVHD should be changed on the basis of infiltrating cell type.