Tanaka S
Dept. of Neurosurgery, Tottori University Medical School.
Gan To Kagaku Ryoho. 1990 Jun;17(6):1157-64.
The therapeutic potential of interleukin 1 (IL-1) in the treatment of malignant glioma was investigated. The direct effect of recombinant human IL-1 beta (rHuIL-1 beta) on cultured U-373 MG glioma cell was evaluated in vitro by BrdU uptake assay, and these effects were compared with those of human interferon beta (HuIFN-beta). Though a growth inhibition and an increase of the percentage of process bearing cells were observed with rHuIL-1 beta at a concentration of 100 ng/ml, these in vitro effects of rHuIL-1 beta were less than those of HuIFN-beta at the same concentrations. Prevention of and enhanced recovery from myelosuppression caused by ACNU by rHuIL-1 beta were evaluated in BALB/c mice. Intravenous injection of ACNU at a dose of 60 mg/kg caused marked decreases in the number of leukocytes, neutrophils, reticulocytes and thrombocytes after seven days. Pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single i.p. injection had a significant preventive effect on these myelosuppression including thrombocytopenia. Enhanced recovery by rHuIL-1 beta administrated seven days after injection of ACNU was also observed. Experimental combination immunochemotherapy with ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. More than 60 mg/kg of ACNU given intraperitoneally inhibited the growth of human glioblastoma in nude mice, but had no effect on survival time of nude mice. The antitumor effect of ACNU was significantly augmented by coadministration of 1 microgram/mouse rHuIL-1 beta. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of ACNU with rHuIL-1 beta. These results suggest that the combined use of IL-1 with chemotherapeutic agents seems to be desirable for clinical application in the treatment of patient with malignant gliomas from the viewpoints of the direct anti-tumor effect, the enhancement of the host immunity, and the prevention of myelosuppression caused by those agents.
研究了白细胞介素1（IL-1）在治疗恶性胶质瘤方面的治疗潜力。通过BrdU摄取试验在体外评估重组人IL-1β（rHuIL-1β）对培养的U-373 MG胶质瘤细胞的直接作用，并将这些作用与人类干扰素β（HuIFN-β）的作用进行比较。尽管在浓度为100 ng/ml时观察到rHuIL-1β可抑制生长并增加有突起细胞的百分比，但rHuIL-1β在相同浓度下的这些体外作用小于HuIFN-β。在BALB/c小鼠中评估了rHuIL-1β对ACNU引起的骨髓抑制的预防作用和增强恢复作用。以60 mg/kg的剂量静脉注射ACNU七天后，白细胞、中性粒细胞、网织红细胞和血小板数量显著减少。以1微克/小鼠的剂量单次腹腔注射rHuIL-1β进行预处理对包括血小板减少在内的这些骨髓抑制具有显著的预防作用。在注射ACNU七天后给予rHuIL-1β也观察到恢复增强。在皮下接种人胶质母细胞瘤的裸鼠中进行了ACNU与rHuIL-1β联合免疫化学治疗的实验。腹腔内给予超过60 mg/kg的ACNU可抑制裸鼠中人胶质母细胞瘤的生长，但对裸鼠的存活时间没有影响。联合给予1微克/小鼠的rHuIL-1β可显著增强ACNU的抗肿瘤作用。在ACNU与rHuIL-1β联合使用时也观察到荷瘤裸鼠存活时间的延长。这些结果表明，从直接抗肿瘤作用、增强宿主免疫力以及预防这些药物引起的骨髓抑制的角度来看，IL-1与化疗药物联合使用似乎适合用于恶性胶质瘤患者的临床治疗。
