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

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 Researchers considering use of this database for publication purposes should contact the first author: [e-mail] Background 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. Material and Methods An exploratory analysis was done on a trial examining the analgesic properties of corticosteroids in patients with advanced cancer. Inclusion criteria were: >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. Results 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 (rs: 0.38-0.41, p Conclusion 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.

参考文献：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》，PLoS ONE，12(5): e0177620。DOI: 10.1371/journal.pone.0177620
若研究者计划使用本数据库开展发表类研究，请联系第一作者：[e-mail]

摘要
背景 全身炎症与晚期癌症患者生活质量下降及症状加重相关。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上述PROMs的变化相关。

材料与方法 本研究针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开展探索性分析。纳入标准为：年龄＞18岁，因中重度癌痛使用阿片类药物镇痛；疼痛评分≥4分（数字疼痛评分量表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核心30项（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（Spearman Rho-Rank）及多元回归分析探讨PROMs与炎症生物标志物之间的关联。

结果 共纳入49例患者的有效数据。sTNF-r1、IL-6、IL-18、MIF、MCP-1、TGF-β1、IL-1ra、C反应蛋白（C-reactive protein，CRP）及红细胞沉降率（Erythrocyte sedimentation rate，ESR）水平升高；IL-1β、IL-2、IL-4、IL-8、IL-10、IL-12(p70)、干扰素-γ、MIP-1α及TNF-α水平低于检测限。本研究观察到以下关联：食欲与IL-6、CRP相关；疲劳与IL-1ra相关（rs: 0.38-0.41, p

结论 在晚期癌症伴疼痛患者中，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。未来可开展旨在探索全身炎症反应缓解及其对症状潜在影响的相关研究。