title: Prospective study evaluating the plasma concentrations of twenty-six cytokines and response to morphine treatment in cancer patients.
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-γ, 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 1α (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.
authors.affiliation: Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Makimura
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takeda
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kiyota
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.forename: Masatomo
authors.initials: M
authors.lastname: Otsuka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Koyama
authors.forename: Chiyo K
authors.initials: CK
authors.lastname: Imamura
authors.forename: Takeharu
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D054405:Chemokine CCL3 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018664:Interleukin-12 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use*; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D054405:Chemokine CCL3; D016207:Cytokines; D018664:Interleukin-12; D009020:Morphine