International Journal of Hematology

, Volume 88, Issue 4, pp 396–402

Stromal cells in bone marrow play important roles in pro-inflammatory cytokine secretion causing fever following bortezomib administration in patients with multiple myeloma

  • Dai Maruyama
  • Takashi Watanabe
  • Yuji Heike
  • Kumiko Nagase
  • Noriko Takahashi
  • Satoshi Yamasaki
  • Fusako Waki
  • Hiroki Yokoyama
  • Sung-Won Kim
  • Yukio Kobayashi
  • Shin Aizawa
  • Kensei Tobinai
Original Article

DOI: 10.1007/s12185-008-0194-0

Cite this article as:
Maruyama, D., Watanabe, T., Heike, Y. et al. Int J Hematol (2008) 88: 396. doi:10.1007/s12185-008-0194-0

Abstract

Bortezomib blocks the activation of nuclear factor-κB-mediated pro-inflammatory cytokines, however, systemic inflammatory symptoms following bortezomib administration have been reported, although their mechanisms remain elusive. Serum samples were obtained from five patients, who participated in a phase I/II study of Japanese patients with relapsed or refractory multiple myeloma (MM), and developed cyclic fever following bortezomib administration, to measure cytokine levels. Significant correlations between interleukin (IL)-6 or interferon (IFN)-γ and the body temperature were observed in two patients each. Furthermore, we found that IL-6 elevation was not observed after the addition of bortezomib to any examined MM cells alone, but was noted in a case of bone marrow stromal cells (BMSCs) of macrophage origin alone or co-cultured with MM cells. Similarly, a marked increase in IFN-γ levels was induced by adding bortezomib to BMSCs of fibroblast origin. Although this investigation was a preliminary study with a small number of patients, our results suggested that pro-inflammatory cytokines causing bortezomib-associated fever were secreted from BMSCs rather than MM cells.

Keywords

Multiple myelomaBortezomibBone marrow stromal cellsPro-inflammatory cytokineIL-6IFN-γ

Copyright information

© The Japanese Society of Hematology 2008

Authors and Affiliations

  • Dai Maruyama
    • 1
  • Takashi Watanabe
    • 1
  • Yuji Heike
    • 1
  • Kumiko Nagase
    • 1
  • Noriko Takahashi
    • 1
  • Satoshi Yamasaki
    • 1
  • Fusako Waki
    • 1
  • Hiroki Yokoyama
    • 1
  • Sung-Won Kim
    • 1
  • Yukio Kobayashi
    • 1
  • Shin Aizawa
    • 2
  • Kensei Tobinai
    • 1
  1. 1.Hematology and Stem Cell Transplantation DivisionNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Functional MorphologyNihon University School of MedicineTokyoJapan