Morinaga H, Tazawa K, Tagoh H, Muraguchi A, Fujimaki M
Second Department of Surgery, Toyama Medical and Pharmaceutical University.
Jpn J Cancer Res. 1994 Dec;85(12):1298-303. doi: 10.1111/j.1349-7006.1994.tb02943.x.
The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The two BRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase-polymerase chain reaction (RT-PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)-1 beta expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL-1 beta levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL-1 beta is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL-1 beta production by liver macrophages, and the produced IL-1 beta activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL-1 beta by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.
在实验动物中研究了口服生物反应调节剂（BRM）预防原发性结直肠癌术后微小肝转移的效果。所测试的两种BRM分别是云芝多糖K（PSK）和香菇菌丝体（LEM）。在先前的实验中，我们发现口服PSK或LEM可抑制肝转移并延长生存期。我们还发现这些药物可提高肝脏自然杀伤（NK）细胞活性和肝脏巨噬细胞活性。在本体内研究中，我们使用逆转录聚合酶链反应（RT-PCR）检测肝脏和脾脏是否具有可诱导NK细胞和巨噬细胞的细胞因子，以及肝脏和脾脏是否具有由NK细胞或巨噬细胞诱导产生的细胞因子。我们重点检测了体内肝脏和脾脏中白细胞介素（IL）-1β的表达。给小鼠口服PSK或LEM（1 g/kg）后2至6小时，肝脏和脾脏中的IL-1β水平升高，24小时后恢复至基线水平。这些发现提示两种可能性：（1）给药后不久这些药物增强了肝脏IL-1β的作用，从而导致肝脏NK细胞或巨噬细胞激活；或（2）这些药物刺激肝脏巨噬细胞产生IL-1β，所产生的IL-1β激活肝脏NK细胞或肝脏巨噬细胞（库普弗细胞）。该体内研究结果提示，PSK和LEM对肝脏和脾脏IL-1β的增强作用参与了结直肠癌微小肝转移抑制的早期阶段。
