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Stromal cells in bone marrow play important roles in pro-inflammatory cytokine secretion causing fever following bortezomib administration in patients with multiple myeloma.
- Source :
-
International journal of hematology [Int J Hematol] 2008 Nov; Vol. 88 (4), pp. 396-402. Date of Electronic Publication: 2008 Nov 07. - Publication Year :
- 2008
-
Abstract
- Bortezomib blocks the activation of nuclear factor-kappaB-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)-gamma 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-gamma 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.
- Subjects :
- Adult
Aged
Antineoplastic Agents administration & dosage
Boronic Acids administration & dosage
Bortezomib
Cell Line, Tumor
Cytokines metabolism
Female
Humans
Male
Middle Aged
Multiple Myeloma drug therapy
Pyrazines administration & dosage
Stromal Cells metabolism
Antineoplastic Agents adverse effects
Bone Marrow Cells metabolism
Boronic Acids adverse effects
Cytokines blood
Fever blood
Fever chemically induced
Inflammation Mediators blood
Multiple Myeloma blood
Pyrazines adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1865-3774
- Volume :
- 88
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 18989635
- Full Text :
- https://doi.org/10.1007/s12185-008-0194-0