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Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma

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Abstract

Transient inflammatory reactions have been reported in a subpopulation of patients with multiple myeloma (MM) during lenalidomide (Len) plus dexamethasone (DEX) therapy. Here, we examined serum levels of Th1 (IL-2 and IFN-γ) and Th2 cytokines (IL-6 and TNF-α) in nine refractory or relapsed MM patients treated with Len plus low-dose DEX. Six patients showed elevation of C-reactive protein (CRP) after the initiation of therapy. In these patients, IFN-γ and IL-6 were also elevated in two and three patients, respectively. The remaining three patients showed no appreciable changes in CRP or these cytokines. Furthermore, Len enhanced the production of both Th1 and Th2 cytokines in normal peripheral blood mononuclear cells and in patient bone marrow mononuclear cells containing primary myeloma cells and lymphocytes. These results suggest that the modulation of the Th1 and Th2 cytokine production by Len may contribute to transient inflammatory reaction in MM patients.

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Acknowledgments

The authors thank Celgene Corporation for providing lenalidomide.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, University of Tokushima, 3-8-15 Kuramoto, Tokushima, 770-8503, Japan

    Takeshi Harada, Shuji Ozaki, Asuka Oda, Shiro Fujii, Shingen Nakamura, Hirokazu Miki, Kumiko Kagawa, Kyoko Takeuchi, Toshio Matsumoto & Masahiro Abe

  2. Division of Transfusion Medicine, Tokushima University Hospital, Tokushima, Japan

    Hirokazu Miki

  3. Department of Hematology, Tokushima Prefectural Central Hospital, Tokushima, Japan

    Shuji Ozaki

Authors
  1. Takeshi Harada
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  2. Shuji Ozaki
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  3. Asuka Oda
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  4. Shiro Fujii
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  5. Shingen Nakamura
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  6. Hirokazu Miki
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  7. Kumiko Kagawa
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  8. Kyoko Takeuchi
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  9. Toshio Matsumoto
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  10. Masahiro Abe
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Corresponding author

Correspondence to Takeshi Harada.

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Fig3

Supplementary Figure 1. Cytokine production by intracellular flow cytometric assay. RPMI 8226 and normal PBMCs in the co-culture setting (A) or patient BMMCs (B) were stimulated by Len for 48 h. Then, intracellular cytokine production was determined by flow cytometry. Representative data are shown from three independent experiments. (JPG 78.6 kb)

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Harada, T., Ozaki, S., Oda, A. et al. Association of Th1 and Th2 cytokines with transient inflammatory reaction during lenalidomide plus dexamethasone therapy in multiple myeloma. Int J Hematol 97, 743–748 (2013). https://doi.org/10.1007/s12185-013-1321-0

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  • DOI: https://doi.org/10.1007/s12185-013-1321-0

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