Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy
Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy
复制标题
DOI：
10.1016/j.cyto.2003.10.004
复制
发表时间：
2004-02-07
期刊：
影响因子：
3.8
通讯作者：
Hortobagyi, GN
中科院分区：
文献类型：
--
作者：
Pusztai, L;Mendoza, TR;Hortobagyi, GN
背景：流感样症状是常见的，紫杉醇化疗的早期短暂副作用。我们假设这些症状可能是由于治疗反应中炎症细胞因子的释放。本研究的目的是评估化疗期间血浆白细胞介素(IL)-1 β、IL-6、IL-8、IL-10、IL-12和tnf - α水平的变化，并将这些变化与肌肉骨骼症状联系起来。方法：90例乳腺癌患者；70例患者每周或每3周接受单药紫杉醇化疗，20例患者接受FAC （5-FU、阿霉素、环磷酰胺）化疗。15名健康志愿者作为对照。在开始治疗前、第3天和一个治疗周期的最后一天测量细胞因子和症状。结果：在基线时，所有受试者的血浆中都有可测量的IL-8水平，但只有49%的人有IL-12, 45%的人有IL-10, 32%的人有IL-6, 21%的人有il -1 β或tnf - α。癌症患者和健康志愿者的基线细胞因子水平没有差异。在紫杉醇治疗的患者中，观察到3种细胞因子水平的时间表依赖性瞬时变化。在每3周紫杉醇组中，IL-6和IL-8升高，而在每周紫杉醇组中，IL-10与基线相比显著升高。疲劳和流感样症状也在第3天加重。在每周紫杉醇组，IL-10水平升高与关节疼痛呈正相关（p = 0.003）。每3周紫杉醇组IL-8水平升高与流感样症状呈正相关（p = 0.008）。在facc治疗组和健康志愿者中，这些细胞因子都没有显著增加。结论：每周紫杉醇治疗可引起血浆IL-10水平的短暂性升高，而每3周高剂量紫杉醇治疗可引起血浆IL-8和1L-6水平的升高。这些变化与关节疼痛和流感样症状有关。(C) 2003 Elsevier Ltd.版权所有。
Background: Flu-like symptoms are common, early transient side effects of paclitaxel chemotherapy. We hypothesized that these symptoms may be due to release of inflammatory cytokines in response to treatment. The objective of this study was to assess changes in plasma levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12, and TNF-alpha during chemotherapy and to correlate these changes with musculoskeletal symptoms.Methods: Ninety patients with breast cancer were included; 70 patients received single agent paclitaxel either weekly or every 3 weeks and 20 received FAC (5-FU, doxorubicin, cyclophosphamide) chemotherapy. Fifteen healthy volunteers were included as controls. Cytokines and symptoms were measured before starting therapy, on day 3 and on the last day of one treatment cycle.Results: At baseline, all subjects had measurable levels of IL-8 but only 49% had IL-12, 45% had IL-10, 32% had IL-6, and 21% had IL-1beta or TNF-alpha in their plasma. There was no difference in baseline cytokine levels between cancer patients and the healthy volunteers. Schedule-dependent transient changes in the levels of 3 cytokines were observed in the paclitaxel treated patients. In the every 3-week paclitaxel group, IL-6 and IL-8 increased whereas in the weekly paclitaxel group IL-10 increased significantly compared to baseline. Fatigue and flu-like symptoms were also worse on day 3. In the weekly paclitaxel group, increase in IL-10 level correlated positively with joint pain (p = 0.003). In the every 3-week paclitaxel group, increase in IL-8 level correlated positively with flu-like symptom (p = 0.008). In the FAC-treated group and among the healthy volunteers none of these cytokines increased significantly.Conclusion: Weekly paclitaxel induces transient increase in IL-10 levels whereas every 3-week higher dose treatments induce IL-8 and 1L-6 in the plasma. These changes correlate with joint pain and flu-like symptoms. (C) 2003 Elsevier Ltd. All rights reserved.