Bouwens L, Marinelli A, Kuppen P J, Eggermont A M, van de Velde C J, Wisse E
Laboratory of Cell Biology and Histology, Free University Brussels (VUB), Belgium.
Hepatology. 1990 Dec;12(6):1365-70. doi: 10.1002/hep.1840120618.
Treatment schedules were investigated for in vivo induction of lymphokine-activated killer cells in the rat liver. Treatment of rats with continuous systemic or regional infusion of recombinant human interleukin-2 with a dose of 4 to 8 x 10(4) U/day during 7 days, resulted in an increase in number of large granular lymphocytes or pit cells in the liver up to 43 times normal. Kupffer cells, nongranular lymphocytes, monocytes and neutrophils also increased in number, but with a maximal fivefold increase this was much less pronounced than for large granular lymphocytes. Kupffer cells showed morphological signs of activation and were frequently seen in mitosis. Frequent mitoses were also observed for large granular lymphocytes, but not for other leukocytes. This indicates that the effect of interleukin-2 treatment on hepatic (sinusoidal) cells was primarily directed to large granular lymphocytes and Kupffer cells. The large granular lymphocyte accumulation occurred mainly intrasinusoidally, but they were also frequently observed in the space of Disse where they are not found in control rats. This may be explained partly by the observed damage or gaps in the endothelial lining. The intrasinusoidal large granular lymphocytes adhered to the endothelium and to Kupffer cells. Higher responses, for all cell types, were found when interleukin-2 was administered regionally, that is, through the hepatic artery rather than through the systemic route (jugular vein), although the differences were not statistically significant. Doses below 4 x 10(4) U/day did not result in significant increases of large granular lymphocytes in the liver.
研究了在大鼠肝脏中体内诱导淋巴因子激活的杀伤细胞的治疗方案。在7天内连续全身或局部输注剂量为4至8×10⁴U/天的重组人白细胞介素-2来治疗大鼠，导致肝脏中大颗粒淋巴细胞或肝巨噬细胞数量增加至正常水平的43倍。库普弗细胞、无颗粒淋巴细胞、单核细胞和中性粒细胞的数量也增加了，但最多增加五倍，这比大颗粒淋巴细胞的增加要明显少得多。库普弗细胞显示出激活的形态学迹象，并且经常可见有丝分裂。大颗粒淋巴细胞也经常观察到有丝分裂，但其他白细胞则没有。这表明白细胞介素-2治疗对肝脏（窦状隙）细胞的作用主要针对大颗粒淋巴细胞和库普弗细胞。大颗粒淋巴细胞的积聚主要发生在窦状隙内，但在狄氏间隙中也经常观察到，而在对照大鼠中则未发现。这可能部分是由于观察到的内皮衬里的损伤或间隙。窦状隙内的大颗粒淋巴细胞粘附在内皮细胞和库普弗细胞上。当通过局部给药，即通过肝动脉而不是通过全身途径（颈静脉）给予白细胞介素-2时，所有细胞类型的反应都更高，尽管差异没有统计学意义。每天剂量低于4×10⁴U不会导致肝脏中大颗粒淋巴细胞显著增加。
