Roughneen P T, Kulkarni S, Kumar S C, Kulkarni A D, Fanslow W, Pellis N R, Rowlands B J
Department of Surgery, University of Texas Medical School, Houston 77030.
Surgery. 1988 Nov;104(5):888-93.
Recent studies by this group have demonstrated that hepatocellular integrity is important in the preservation of host cellular immune function. This study evaluated the effect of experimental hepatocellular dysfunction (EHD) on host antineoplastic defense mechanisms. In nonspecific immune studies, we examined the effect of EHD on Wistar Furth (WF) natural killer (NK) cell cytotoxicity; in specific immune studies, we assessed WF C3H/HeJ lymphocytic responsiveness to both T cell mitogen and unmodified syngeneic fibrosarcoma. In concurrent studies, we evaluated the effect of EHD on interleukin-2 (IL-2) synthesis, an important NK and T cell trophic factor. WF rats and C3H/HeJ mice were assigned to three groups: EHD induced by bile duct ligation, sham, and normal control (NC). At day 21 serum bilirubin, WF NK cytotoxicity to YAC-1 tumor cells, WF and C3H/HeJ lymphocytic responsiveness to phytohemagglutinin (PHA) and syngeneic MCA-fibrosarcoma (MCA-F), and WF T-helper IL-2 production were determined in respective groups. Serum total bilirubin was elevated in EHD rats and mice with respect to controls (p less than 0.01). Wistar Furth cytotoxicity to the YAC-1 tumor cells was depressed in EHD animals with respect to sham and NC groups at 12.5:1 (p less than 0.01), 25:1 (p less than 0.05), 50:1 (p less than 0.05), and 100:1 (p less than 0.05) effector/target cell ratios. WF T cell responsiveness to PHA was depressed in EHD with respect to controls (p less than 0.01). C3H/HeJ lymphoproliferative response to MCA-F tumor antigen was also depressed in EHD animals when compared with control groups with the addition of 12.5 X 10(3) (p less than 0.05) and 50 X 10(3) (p less than 0.05) MCA-F cells. These impairments in NK and T cell function in EHD could not be attributed to diminished IL-2 production (EHD vs sham and NC: 112,141 +/- 5232 vs 106,691 +/- 1419 and 120,759 +/- 3248 cpm, respectively). These results demonstrate that hepatocellular failure compromises NK and T cell tumoricidal function, an effect not resultant on diminished T helper IL-2 production.
该研究团队最近的研究表明，肝细胞完整性在维持宿主细胞免疫功能方面很重要。本研究评估了实验性肝细胞功能障碍（EHD）对宿主抗肿瘤防御机制的影响。在非特异性免疫研究中，我们检测了EHD对Wistar Furth（WF）自然杀伤（NK）细胞细胞毒性的影响；在特异性免疫研究中，我们评估了WF C3H/HeJ淋巴细胞对T细胞有丝分裂原和未修饰的同基因纤维肉瘤的反应性。在同期研究中，我们评估了EHD对白细胞介素-2（IL-2）合成的影响，IL-2是一种重要的NK和T细胞营养因子。将WF大鼠和C3H/HeJ小鼠分为三组：胆管结扎诱导的EHD组、假手术组和正常对照组（NC）。在第21天，分别测定各组的血清胆红素、WF对YAC-1肿瘤细胞的NK细胞毒性、WF和C3H/HeJ淋巴细胞对植物血凝素（PHA）和同基因MCA-纤维肉瘤（MCA-F）的反应性，以及WF辅助性T细胞IL-2的产生。与对照组相比，EHD大鼠和小鼠的血清总胆红素升高（p<0.01）。在效应细胞/靶细胞比例为12.5:1（p<0.01）、25:1（p<0.05）、50:1（p<0.05）和100:1（p<0.05）时，EHD动物中WF对YAC-1肿瘤细胞的细胞毒性相对于假手术组和NC组降低。与对照组相比，EHD组中WF T细胞对PHA的反应性降低（p<0.01）。当加入12.5×10³（p<0.05）和50×10³（p<0.05）个MCA-F细胞时，与对照组相比，EHD动物中C3H/HeJ对MCA-F肿瘤抗原的淋巴细胞增殖反应也降低。EHD中NK和T细胞功能的这些损害不能归因于IL-2产生的减少（EHD组与假手术组和NC组相比：分别为112,141±5232、106,691±1419和120,759±3248 cpm）。这些结果表明，肝细胞衰竭损害了NK和T细胞的杀肿瘤功能，这种效应并非由辅助性T细胞IL-2产生的减少所致。
