Stromal cells in bone marrow play important roles in pro-inflammatory cytokine secretion causing fever following bortezomib administration in patients with multiple myeloma Authors
First Online: 07 November 2008 Received: 28 December 2007 Revised: 13 August 2008 Accepted: 04 September 2008 DOI:
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 myeloma Bortezomib Bone marrow stromal cells Pro-inflammatory cytokine IL-6 IFN-γ References
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