Jonsdottir I H, Johansson C, Asea A, Hellstrand K, Thorén P, Hoffmann P
Department of Physiology, Göteborg University, Sweden.
Regul Pept. 1996 Apr 23;62(2-3):113-8. doi: 10.1016/0167-0115(96)00007-9.
We have studied the effect of chronic intracerebroventricular (i.c.v.) infusion of different opioid peptides on natural killer (NK) cell mediated cytotoxicity in vivo in the spontaneously hypertensive rat (SHR). The in vivo NK cell activity was measured as the clearance of 51Cr-labelled YAC-l lymphoma cells from the lung tissues. Further, the phenotype of lymphocytes in spleen and peripheral blood was analysed by flow cytometry (FACS). All opioid drugs were administered i.c.v. for 6 days with osmotic minipumps releasing 1.0 microliter/h. beta-Endorphin (10 or 20 micrograms/rat per day) significantly increased NK cell cytotoxicity in vivo. The opioid receptor antagonist naloxone (10 mg/kg, i.p.) given immediately before the injection of YAC-lymphoma cells, completely abolished the effects of i.c.v. administered beta-endorphin. Corresponding doses of beta-endorphin administered subcutaneously (s.c.) with minipumps for 6 days did not significantly affect NK cell cytotoxicity. Neither Leu- or Met-enkephalin (20 micrograms/rat per day) nor dynorphin (20 micrograms/rat per day) administered i.c.v. had any significant effects on NK cell activity. In beta-endorphin treated SHR, the percentage of cells with NK cell phenotype (OX52+/CD5-) in peripheral blood was not significantly different from that of controls, while the percentage of cells with T cell phenotype (CD5+/OX52-) was significantly decreased. The percentage of splenic NK cells (OX52+/CD5-) and T cells (CD5+/OX52-) was also unchanged by beta-endorphin treatment i.c.v. These results suggest that of the opioid peptides administered i.c.v., only beta-endorphin augments in vivo NK cell mediated cytotoxicity. We thus conclude that these effects most probably are centrally and opioid receptor mediated effects, since beta-endorphin in the same dose administered peripherally does not influence in vivo NK cell cytotoxicity.
我们研究了慢性脑室内（i.c.v.）注入不同阿片肽对自发性高血压大鼠（SHR）体内自然杀伤（NK）细胞介导的细胞毒性的影响。体内NK细胞活性通过测量肺组织中51Cr标记的YAC-1淋巴瘤细胞的清除率来测定。此外，通过流式细胞术（FACS）分析脾脏和外周血中淋巴细胞的表型。所有阿片类药物均通过渗透微型泵以每小时1.0微升的速度i.c.v.给药6天。β-内啡肽（每天10或20微克/大鼠）显著增加体内NK细胞的细胞毒性。在注射YAC淋巴瘤细胞之前立即腹腔注射（i.p.）阿片受体拮抗剂纳洛酮（10毫克/千克），完全消除了i.c.v.给予的β-内啡肽的作用。用微型泵皮下（s.c.）给予相应剂量的β-内啡肽6天，对NK细胞细胞毒性没有显著影响。i.c.v.给予的亮氨酸脑啡肽或甲硫氨酸脑啡肽（每天20微克/大鼠）以及强啡肽（每天20微克/大鼠）对NK细胞活性均无显著影响。在β-内啡肽处理的SHR中，外周血中具有NK细胞表型（OX52+/CD5-）的细胞百分比与对照组无显著差异，而具有T细胞表型（CD5+/OX52-）的细胞百分比显著降低。i.c.v.给予β-内啡肽处理后，脾脏NK细胞（OX52+/CD5-）和T细胞（CD5+/OX52-）的百分比也没有变化。这些结果表明，在i.c.v.给予的阿片肽中，只有β-内啡肽能增强体内NK细胞介导的细胞毒性。因此，我们得出结论，这些作用很可能是中枢性和阿片受体介导的作用，因为外周给予相同剂量的β-内啡肽不会影响体内NK细胞的细胞毒性。
