Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
Anticancer Res. 2011 Dec;31(12):4561-8.
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.
细胞因子信号参与疼痛和阿片受体信号。在这项前瞻性研究中，我们研究了血浆细胞因子水平，以鉴定预测阿片类药物治疗-naive 癌症患者吗啡治疗耐药的候选生物标志物。我们使用多指标免疫分析系统分析了基线时和吗啡治疗后疼痛评分和 26 种细胞因子的血浆浓度，用于分析的细胞因子包括：嗜酸性粒细胞趋化因子、集落刺激因子、粒细胞 (G-CSF)、集落刺激因子粒细胞-巨噬细胞 (GM-CSF)、干扰素 α2 (IFN-α2)、干扰素-γ、白细胞介素 1α (IL-1α)、白细胞介素 1β (IL-1β)、白细胞介素 2 (IL-2)、白细胞介素 3 (IL-3)、白细胞介素 4 (IL-4)、白细胞介素 5 (IL-5)、白细胞介素 6 (IL-6)、白细胞介素 7 (IL-7)、白细胞介素 8 (IL-8)、白细胞介素 10 (IL-10)、白细胞介素 12(p40)、白细胞介素 12(p70)、白细胞介素 13 (IL-13)、白细胞介素 15 (IL-15)、白细胞介素 17 (IL-17)、干扰素诱导蛋白 10 (IP-10)、单核细胞趋化蛋白 1 (MCP-1)、巨噬细胞炎性蛋白 1α (MIP-1α)、巨噬细胞炎性蛋白 1β (MIP-1β)、肿瘤坏死因子-α (TNF-α) 和 TNF-β。基线时疼痛的数字评分量表和发生吗啡治疗耐药的患者之间未观察到临床特征与疼痛的数值评分量表之间存在相关性。有趣的是，MIP-1α 的血浆浓度在吗啡治疗期间显著降低（第 8 天与基线相比，p=0.03）。关于基线时的血浆细胞因子浓度，没有一种细胞因子水平与基线时的疼痛数字评分量表相关；然而，在需要高剂量吗啡或发生吗啡治疗耐药的患者中，基线时的嗜酸性粒细胞趋化因子、IL-8、IL-12(p40)、IL-12(p70)、MIP-1α 和 MIP-1β 的血浆浓度明显降低。总之，这是首次报道表明几种细胞因子的血浆浓度在治疗过程中显著调节，并与吗啡治疗的结果相关。我们的结果表明，血浆细胞因子水平可能是吗啡治疗有前途的生物标志物，值得进一步研究。
