Ahlers Olaf, Hildebrandt Bert, Dieing Annette, Deja Maria, Böhnke Thomas, Wust Peter, Riess Hanno, Gerlach Herwig, Kerner Thoralf
Klinik für Anästhesiologie und operative Intensivmedizin, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13344, Berlin, Germany.
Eur J Appl Physiol. 2005 Oct;95(4):298-306. doi: 10.1007/s00421-005-0009-4. Epub 2005 Oct 27.
Extreme acute physical stress leads to transient impairment of T-lymphocytes, which are essential for tumor defence and prevention of infectious diseases. Radiant whole body hyperthermia (WBH) at 41.8-42.2 degrees C may enhance the efficacy of systemic chemotherapy in patients with advanced malignancies, but is associated with marked physical stress. Aim of this study was to demonstrate stress induced short-time effects on lymphocyte subpopulations and associated cytokines during WBH. Total leukocyte count, white blood cell differential blood count, lymphocyte subpopulations (T-helper-/T4-cells, T-suppressor-/T8-cells, natural-killer-/NK-cells, gammadelta-T-cells) as well as plasma levels of Interleukin(IL)-10, IL-12 and Interferon-gamma (IFN-gamma) were measured in ten patients treated with WBH and additional cytostatic chemotherapy. Blood samples were drawn before treatment, at three temperature points during WBH, and 24 h after start of treatment. Results were compared with those obtained from a control group consisting of six patients receiving chemotherapy alone. Numbers of T4-cells decreased significantly during WBH, while numbers of NK-cells and gammadelta-T-cells increased, resulting in transient impairments of total lymphocyte counts and T4/T8-ratio. IL-12 plasma levels as well as IFN-gamma/IL-10-ratio also decreased during WBH. No significant changes were found in T8-cells of WBH patients. Changes were reversible within 24 h and could not been found in control patients. Our results support the hypothesis that WBH combined with chemo therapy induces a strong but reversible anti-inflammatory stress response in cancer patients during therapy. Further studies are necessary to examine the pathophysiological details and to evaluate the meaning of these transient immunological changes for patient's outcome.
极端急性身体应激会导致T淋巴细胞短暂受损，而T淋巴细胞对肿瘤防御和预防传染病至关重要。41.8 - 42.2摄氏度的全身辐射热疗（WBH）可能会增强晚期恶性肿瘤患者全身化疗的疗效，但会伴有明显的身体应激。本研究的目的是证明热疗期间应激对淋巴细胞亚群和相关细胞因子的短期影响。对10例接受热疗及辅助细胞毒性化疗的患者，测定其全白细胞计数、白细胞分类计数、淋巴细胞亚群（辅助性T/T4细胞、抑制性T/T8细胞、自然杀伤/NK细胞、γδ-T细胞）以及血浆白细胞介素（IL）-10、IL-12和干扰素-γ（IFN-γ）水平。在治疗前、热疗期间的三个温度点以及治疗开始后24小时采集血样。将结果与由6例仅接受化疗的患者组成的对照组所得结果进行比较。热疗期间T4细胞数量显著减少，而NK细胞和γδ-T细胞数量增加，导致总淋巴细胞计数和T4/T8比值短暂受损。热疗期间IL-12血浆水平以及IFN-γ/IL-10比值也降低。热疗患者的T8细胞未发现显著变化。这些变化在24小时内可逆，且在对照患者中未发现。我们的结果支持以下假设：热疗联合化疗在治疗期间会在癌症患者中诱导强烈但可逆的抗炎应激反应。有必要进一步研究以检查病理生理细节，并评估这些短暂免疫变化对患者预后的意义。
