The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer Database

<strong> </strong><strong> </strong>Publication: Paulsen Ø, Laird B, Aass N, Lea T, Fayers P, Kaasa S, et al. (2017) The relationship between pro-inflammatory cytokines and pain, appetite and fatigue in patients with advanced cancer. PLoS ONE 12(5): e0177620. https://doi.org/10.1371/journal.pone.0177620<br> Researchers considering use of this database for publication purposes should contact the first author: [e-mail]<b>Abstract</b> <b>Background</b> Systemic inflammation is associated with reduced quality of life and increased symptoms in patients with advanced cancer. The aims of this study were to examine the relationships between inflammatory biomarkers and the Patient Reported Outcome Measures (PROMs) of pain, appetite and fatigue; and to explore whether levels of baseline biomarkers were associated with changes in these PROMs following treatment with corticosteroids. <b>Material and Methods</b> An exploratory analysis was done on a trial examining the analgesic properties of corticosteroids in patients with advanced cancer. Inclusion criteria were: &gt;18 years, taking opioids for moderate or severe cancer pain; pain ≥4 (numerical rating scale 0-10). Serum was extracted and levels of inflammatory biomarkers were assessed. PROMs of pain, appetite and fatigue were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30). The relationships between PROMs and inflammatory biomarkers were examined using Spearman Rho-Rank and multiple regression analysis. <b>Results</b> Data were available on 49 patients. Levels of sTNF-r1, IL-6, IL-18, MIF, MCP-1, TGF-β1, IL-1ra, and C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) were elevated; IL-1β, IL-2, IL-4, IL-8, IL-10, IL-12(p70), interferon-γ, MIP-1α, and TNF-α were below the level of detection. The following correlations were observed: appetite and IL-6 and CRP; fatigue and IL-1ra (r_s: 0.38-0.41, <i>p</i>&lt; .01). There was no association between pretreatment biomarkers and effect from corticosteroid treatment. <b>Conclusion</b> <b><i>In patients with advanced cancer and pain, some pro-inflammatory cytokines were related to appetite and fatigue. Inflammatory biomarkers were not associated with pain or with the efficacy of corticosteroid therapy. Further research examining the attenuation of the systemic inflammatory response and possible effects on symptoms would be of interest. </i></b><br>** ** ** ** 出版物：Paulsen Ø、Laird B、Aass N、Lea T、Fayers P、Kaasa S 等 (2017) 晚期癌症患者促炎细胞因子与疼痛、食欲及疲劳的相关性研究. PLoS ONE 12(5): e0177620. https://doi.org/10.1371/journal.pone.0177620 拟将本数据库用于发表成果的研究者，请联系第一作者：[e-mail] **摘要** **背景** 全身性炎症与晚期癌症患者生活质量降低及症状加重密切相关。本研究旨在探讨炎症生物标志物与疼痛、食欲及疲劳的患者报告结局指标（Patient Reported Outcome Measures, PROMs）之间的关联，并探索基线生物标志物水平是否与糖皮质激素治疗后这些PROMs的变化存在相关性。 **材料与方法** 本研究对一项评估糖皮质激素对晚期癌症患者镇痛作用的临床试验进行探索性分析。纳入标准为：年龄＞18岁，因中度至重度癌痛使用阿片类药物；疼痛评分≥4（数字评分量表0~10分）。采集血清样本并检测炎症生物标志物水平。采用欧洲癌症研究与治疗组织生活质量问卷-C30（European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, EORTC QLQ-C30）评估疼痛、食欲及疲劳的PROMs。采用斯皮尔曼秩相关分析及多元回归分析检验PROMs与炎症生物标志物之间的相关性。 **结果** 共获取49例患者的有效数据。可溶性肿瘤坏死因子受体1（sTNF-r1）、白细胞介素6（IL-6）、白细胞介素18（IL-18）、巨噬细胞迁移抑制因子（MIF）、单核细胞趋化蛋白1（MCP-1）、转化生长因子β1（TGF-β1）、白细胞介素1受体拮抗剂（IL-1ra）、C反应蛋白（C-reactive protein, CRP）及红细胞沉降率（Erythrocyte sedimentation rate, ESR）水平均升高；而白细胞介素1β（IL-1β）、白细胞介素2（IL-2）、白细胞介素4（IL-4）、白细胞介素8（IL-8）、白细胞介素10（IL-10）、白细胞介素12(p70)、干扰素γ、巨噬细胞炎症蛋白1α（MIP-1α）及肿瘤坏死因子α（TNF-α）水平低于检测下限。观察到以下相关性：食欲与IL-6、CRP相关；疲劳与IL-1ra相关（r_s: 0.38~0.41, *p*<0.01）。治疗前基线生物标志物水平与糖皮质激素治疗的疗效无显著关联。 **结论** <i>在伴有疼痛的晚期癌症患者中，部分促炎细胞因子与食欲及疲劳相关。炎症生物标志物与疼痛或糖皮质激素治疗的疗效无关联。针对全身性炎症反应的缓解及其对症状的潜在影响开展进一步研究，将具有重要学术价值。</i>