Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients

Chihiro Makimura, Tokuzo Arao, Hiromichi Matsuoka, Masayuki Takeda, Hidemi Kiyota, Junji Tsurutani, Yoshihiko Fujita, Kazuko Matsumoto, Hideharu Kimura, Masatomo Otsuka, Atsuko Koyama, Chiyo K. Imamura, Takeharu Yamanaka, Kyoko Tanaka, Kazuto Nishio, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cytokine signaling is involved in pain and opioid-receptor signaling. In this prospective study, we studied the plasma cytokine levels in order to identify candidate biomarkers for predicting resistance to morphine treatment in a cohort of opioid-treatment-naïve cancer patients. We analyzed pain rating and the plasma concentrations of 26 cytokines at baseline and after morphine treatment using a multiplex immunoassay system for the following cytokines: eotaxin, colony stimulating factor, granulocyte (G-CSF), colony stimulating factor granulocyte-macrophage (GM-CSF), interferon α2 (IFN-α2), IFN-α, interleukin 1α (IL-1α), IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p40), IL-12 (p70), IL-13, IL-15, IL-17, IP-10, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein la (MIP-1α), MIP-1β, tumor necrosis factor-α (TNF-α) and TNF-β. No correlation was observed between the clinical characteristics and the numerical rating scale for pain at baseline or among patients who developed resistance to morphine treatment. Interestingly, the plasma concentration of MIP-1α significantly decreased during morphine treatment (day 8 vs. baseline, p=0.03). Regarding the baseline plasma cytokine concentrations, none of the cytokine levels were correlated with the numerical rating scale for pain at baseline; however, the baseline plasma concentrations of eotaxin, IL-8, IL-12 (p40), IL-12 (p70), MIP-1α and MIP-1β were significantly lower in patients who required a high dose of morphine or who developed resistance to morphine treatment. In conclusion, this is the first report revealing that the plasma concentrations of several cytokines were significantly modulated during treatment and were correlated with treatment outcome of morphine. Our results suggest that plasma cytokine levels may be promising biomarkers for morphine treatment and that they warrant further study.

Original languageEnglish
Pages (from-to)4561-4568
Number of pages8
JournalAnticancer research
Volume31
Issue number12
Publication statusPublished - 2011 Dec 1

Keywords

  • Cytokines
  • IL-12
  • MIP-1α
  • Morphine
  • Plasma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Makimura, C., Arao, T., Matsuoka, H., Takeda, M., Kiyota, H., Tsurutani, J., Fujita, Y., Matsumoto, K., Kimura, H., Otsuka, M., Koyama, A., Imamura, C. K., Yamanaka, T., Tanaka, K., Nishio, K., & Nakagawa, K. (2011). Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients. Anticancer research, 31(12), 4561-4568.