Shen R N, Lu L, Young P, Shidnia H, Hornback N B, Broxmeyer H E
Department of Medicine (Hematology-Oncology), Indiana University School of Medicine, Walther Oncology Center, Indianapolis 46202-5121.
Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):821-6. doi: 10.1016/0360-3016(94)90571-1.
To determine whether hyperthermia is to the benefit or detriment of host immune function, the effect of hyperthermia was evaluated on various functions of T-lymphocytes from human umbilical cord blood and compared to that of adult blood.
Nonadherent mononuclear cells from cord blood or adult blood were used as the effector cells. To generate lymphokine activated killer (LAK) cells, effector cells were kept in culture for 5 days in complete medium containing recombinant human interleukin-2. To activate effector cells to become cytotoxic, cells were kept in culture in complete medium containing Con A. Cytotoxicity was determined in a standard 4-h chromium release assay using K-562 human erythroleukemic cells (in the natural killer cell activity assay) or Daudi cells (in the LAK cell activity or Lectin dependent cytotoxicity assay) as targets. For heat effects, cells in complete medium were heated at the desired temperature in a water bath for 1 h.
Lymphokine-activated killer cell activity, lectin-dependent cytotoxicity and T-cell proliferative capacity were not deficient in human cord blood. Cytotoxic activities of T-cells from adult blood as well as from cord blood can be enhanced at febrile range (< or = 40 degrees C), and were significantly decreased by exposure to 1 h at 42 degrees C.
The febrile responses (< or = 40 degrees C) to infection, in the course of malignant disease and with biological response modifiers treatment, may all be related to host defense mechanisms. Based on these observations, whole body hyperthermia (< or = 40 degrees C), in combination with the appropriate cytokines, may have therapeutic potential in the treatment of neonatal infections and malignancies under certain circumstances. Hyperthermia in febrile range may, therefore, confer an important immunoregulatory advantage to the host. In contrast, tumor killing therapeutic temperature (> 42 degrees C) which inhibits host immunocompetence should probably be used only for local hyperthermia.
为了确定热疗对宿主免疫功能是有益还是有害，评估了热疗对人脐带血T淋巴细胞各种功能的影响，并与成人血液进行了比较。
来自脐带血或成人血液的非贴壁单核细胞用作效应细胞。为了产生淋巴因子激活的杀伤（LAK）细胞，将效应细胞在含有重组人白细胞介素-2的完全培养基中培养5天。为了激活效应细胞使其具有细胞毒性，将细胞在含有刀豆蛋白A的完全培养基中培养。使用K-562人红白血病细胞（在自然杀伤细胞活性测定中）或Daudi细胞（在LAK细胞活性或凝集素依赖性细胞毒性测定中）作为靶标，通过标准的4小时铬释放试验测定细胞毒性。对于热效应，将完全培养基中的细胞在水浴中于所需温度加热1小时。
人脐带血中淋巴因子激活的杀伤细胞活性、凝集素依赖性细胞毒性和T细胞增殖能力并不缺乏。成人血液和脐带血中T细胞的细胞毒性活性在发热范围（≤40℃）可增强，而在42℃暴露1小时后显著降低。
在恶性疾病过程中以及使用生物反应调节剂治疗时，对感染的发热反应（≤40℃）可能都与宿主防御机制有关。基于这些观察结果，全身热疗（≤40℃）与适当的细胞因子联合使用，在某些情况下可能对新生儿感染和恶性肿瘤具有治疗潜力。因此，发热范围内的热疗可能为宿主带来重要的免疫调节优势。相比之下，抑制宿主免疫能力的肿瘤杀伤治疗温度（>42℃）可能仅应仅用于局部热疗。
