Lin J C, Park H J, Song C W
University of Minnesota Medical School, Department of Therapeutic Radiology-Radiation Oncology, Minneapolis, Minnesota 55455, USA.
Int J Hyperthermia. 1996 May-Jun;12(3):335-44. doi: 10.3109/02656739609022522.
Vasoactive cytokines, such as IL-1 alpha and TNF-alpha, modulate the homeostatic state at the endothelial surface and cause various types of pathological damage in vascular systems. We investigated the potential therapeutic effects of IL-1 alpha and TNF-alpha in combination with hyperthermia on SCK tumours grown in the legs of A/J mice. We first determined the effect of cytokines on tumour blood perfusion with the (86)Rb uptake method. When the host mice were given an i.p. injection of 25 mu g/kg IL-1 alpha or 50 mu g/kg TNF-alpha, the tumour blood perfusion markedly declined to 46 and 82% of control, respectively. The combination of IL-1 alpha and TNF-alpha reduced the 86Rb uptake to 41% bf control. Hyperthermia at 42.5 degrees C for 1 h reduced the tumour blood flow to 71% of control. The tumour blood perfusion decreased further to 20% of control when the tumours were heated for 1 h at 42.5 degrees C starting 4h after the injection of both IL-1 alpha and TNF-alpha. The changes in clonogenic cell numbers in SCK tumours, as determined by the in vivo-in vitro assay, following various treatments was also investigated. At 4 h after an i.p. injection of 25 mu g/kg IL-1 alpha or 50 mu g/kg TNF-alpha, the clonogenicity of SCK tumours significantly decreased to 29 or 37% of control, respectively. Heating at 42.5 degrees C for 1 h caused a decline in the clonogenic cell number to 30% of control. When both IL-1 alpha and TNF-alpha were given and tumours were heated 4h later at 42.5 degrees C for 1 h, the clonogenic cell number markedly declined to 0.4% of control. The time needed for control tumours to reach 4 x their initial volume was about 3 days, and treatment with IL-1 alpha or hyperthermia alone induced a tumour delay growth by about 1 day. The combined injection of IL-1 alpha and TNF-alpha followed by a heating at 42.5 degrees C for 1 h delayed the tumour growth by 6 days. The results in this study suggest that prior impairment of blood circulation by the combined treatment of IL-1 alpha and TNF-alpha potentiates hyperthermic damage in tumours.
血管活性细胞因子，如白细胞介素-1α（IL-1α）和肿瘤坏死因子-α（TNF-α），可调节内皮表面的稳态，并在血管系统中引发各种类型的病理损伤。我们研究了IL-1α和TNF-α与热疗联合应用对A/J小鼠腿部生长的SCK肿瘤的潜在治疗效果。我们首先用（86）Rb摄取法确定细胞因子对肿瘤血液灌注的影响。当给宿主小鼠腹腔注射25μg/kg的IL-1α或50μg/kg的TNF-α时，肿瘤血液灌注分别显著下降至对照的46%和82%。IL-1α和TNF-α联合使用使86Rb摄取降至对照的41%。42.5℃热疗1小时可使肿瘤血流量降至对照的71%。当在注射IL-1α和TNF-α后4小时开始在42.5℃加热肿瘤1小时，肿瘤血液灌注进一步降至对照的20%。还研究了通过体内-体外试验测定的各种处理后SCK肿瘤中克隆形成细胞数量的变化。腹腔注射25μg/kg的IL-1α或50μg/kg的TNF-α后4小时，SCK肿瘤的克隆形成能力分别显著下降至对照的29%或37%。42.5℃加热1小时导致克隆形成细胞数量降至对照的30%。当同时给予IL-1α和TNF-α，4小时后在42.5℃加热肿瘤1小时，克隆形成细胞数量显著下降至对照的0.4%。对照肿瘤达到其初始体积4倍所需的时间约为3天，单独用IL-1α或热疗治疗可使肿瘤生长延迟约1天。先联合注射IL-1α和TNF-α，然后在42.5℃加热1小时，可使肿瘤生长延迟6天。本研究结果表明，IL-1α和TNF-α联合治疗预先损害血液循环可增强热疗对肿瘤的损伤。
