Atanackovic Djordje, Pollok Kristina, Faltz Christiane, Boeters Ina, Jung Roman, Nierhaus Alexander, Braumann Klaus-Michael, Hossfeld Dieter Kurt, Hegewisch-Becker Susanna
Department of Oncology/Hematology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Am J Physiol Regul Integr Comp Physiol. 2006 Mar;290(3):R585-94. doi: 10.1152/ajpregu.00014.2005. Epub 2005 Oct 27.
An activation of the immune system might contribute to the therapeutic effect of whole body hyperthermia (WBH) in cancer patients. We explored immune and endocrine responses in patients undergoing high-temperature WBH. Identical parameters were investigated in a separate group of healthy volunteers undergoing physical exercise to rule out effects of sympathetic activation. Lymphocyte subpopulations, lymphocytic expression of a range of adhesion molecules, and serum concentrations of a variety of hormones and cytokines were assessed in cancer patients undergoing high-temperature (60 min at 41.0-41.8 degrees C) WBH (n = 25) and in a separate group of healthy volunteers (n = 10) performing strenuous physical exercise. WBH induced an increase in human growth hormone (hGH), ACTH, and cortisol as well as in TNF-alpha, IL-6, IL-8, and IL-12R. We observed an increase in natural killer (NK) cells and CD56+ NK T cells shortly after initiation of WBH. In contrast, we found a decrease in T cells expressing L-selectin (CD62L) or alpha4beta7 integrin adhesion molecules mediating homing to lymphatic tissues. Accordingly, we observed a decrease in CD45RA+CCR7+ naive and CD45RA-CCR7+ central memory T cells. Numbers of CD45RA-CCR7- memory effector and CD45RA+CCR7 terminally differentiated T cells, on the other hand, remained unchanged. No comparable changes were observed in the group of healthy volunteers. In conclusion, patients with solid tumors treated with WBH show an increase in NK and NK T cells. In a later phase, plasma concentrations of IL-8, hGH, and cortisol increase, correlated with an influx of neutrophils into the peripheral blood. The alterations in T-cell populations suggest that WBH may induce naive and central-memory T cells to enter lymphatic tissue to await antigen exposure and effector T cells to migrate into peripheral tissues to exert their effector function. Although the exercise group may not be an appropriate control to proof the effect of WBH, these changes were not seen in the healthy volunteers performing physical exercise.
免疫系统的激活可能有助于全身热疗(WBH)对癌症患者的治疗效果。我们探究了高温WBH患者的免疫和内分泌反应。在另一组进行体育锻炼的健康志愿者中研究相同参数,以排除交感神经激活的影响。对接受高温(41.0 - 41.8摄氏度,持续60分钟)WBH的癌症患者(n = 25)和另一组进行剧烈体育锻炼的健康志愿者(n = 10)评估淋巴细胞亚群、一系列黏附分子的淋巴细胞表达以及多种激素和细胞因子的血清浓度。WBH诱导人类生长激素(hGH)、促肾上腺皮质激素(ACTH)和皮质醇以及肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-12受体(IL-12R)增加。我们观察到WBH开始后不久自然杀伤(NK)细胞和CD56 + NK T细胞增加。相反,我们发现表达介导归巢至淋巴组织的L-选择素(CD({}_{62})L)或α4β7整合素黏附分子的T细胞减少。因此,我们观察到CD45RA + CCR7 + 初始T细胞和CD45RA - CCR7 + 中央记忆T细胞减少。另一方面,CD45RA - CCR7 - 记忆效应T细胞和CD45RA + CCR7终末分化T细胞数量保持不变。在健康志愿者组中未观察到类似变化。总之,接受WBH治疗的实体瘤患者的NK和NK T细胞增加。在后期,IL-8、hGH和皮质醇的血浆浓度增加,与中性粒细胞流入外周血相关。T细胞群体的改变表明WBH可能诱导初始T细胞和中央记忆T细胞进入淋巴组织等待抗原暴露,效应T细胞迁移到外周组织发挥其效应功能。尽管运动组可能不是证明WBH效果的合适对照组,但在进行体育锻炼的健康志愿者中未观察到这些变化。