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

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)396-402
Number of pages7
JournalInternational journal of hematology
Volume88
Issue number4
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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