Small doses of morphine can enhance NK cell cytotoxicity in pigs
Small doses of morphine can enhance NK cell cytotoxicity in pigs
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DOI：
10.1016/j.intimp.2008.11.006
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发表时间：
2009-03-01
影响因子：
5.6
通讯作者：
Tokarski, Juliusz
中科院分区：
文献类型：
--
作者：
Borman, Andrzej;Ciepielewski, Ziemowit;Tokarski, Juliusz
本文观察了小剂量和中等剂量吗啡(MF)对静脉置管皮特兰杂交猪NK细胞杀伤活性(NKCC)(Cr-51释放试验)和循环大颗粒淋巴细胞(LGL)数量的影响。同时测定血浆皮质醇(COR)(RIA法)。静脉注射后15分钟、50分钟、120分钟、180分钟、240分钟采血。分别注射0.5、1.0、5.0 mg/kg的MF或用纳洛酮预先处理的MF(NX，1.0 mg/kg，静脉注射，MF前15分钟)。结果表明，MF可引起NKCC的剂量和时间依赖性改变。0.5 mg/kg剂量的MF可使NKCC数增加4倍(与生理盐水相比)，但对LGL/NK细胞数无明显影响。较高的MF剂量(1.0.5.0 mg/kg可引起早期细胞毒性增加(分别高达300Delta%和29Delta%)，随后细胞毒性降低(5.0 mg/kg后达-76Delta%)，LGL数减少(5.0 mg/kg后为-36Delta%)。伴随着这些效应的是血浆COR显著升高(0.5 mg/kg后高达234 Delta%，5.0 mg/kg后高达567 Delta%)。NX处理可阻断LGL细胞毒性的所有变化，但不能阻断LGL细胞数量和COR浓度的变化。结果表明，MF除了具有免疫抑制作用外，还可通过阿片受体依赖的方式增强NKCC。细胞毒性的增强似乎是一种纯粹的功能变化，与NK细胞的再循环无关，尽管血浆中存在较高的COR浓度。(C)2008爱思唯尔B.V.保留所有权利。
The effect of small and moderate doses of morphine (MF) on NK cell lytic activity (cytotoxicity, NKCC) (Cr-51 release test) and the number of circulating large granular lymphocytes (LGL) was evaluated in i.v, catheterized Pietrain crossbred pigs. Simultaneously, plasma cortisol (COR) (RIA method) was measured. Blood samples were collected 15, 50,120,180, and 240 min after i.v. injections of 0.5, 1.0 and 5.0 mg/kg of MF alone or MF pretreated with naloxone (NX,1.0 mg/kg, i.v,15 min before MF). It was found that MF induced dose- and time-dependent changes of NKCC. MF in a dose of 0.5 mg/kg evoked 4-fold increase in NKCC (in comparison to saline) without changes in the number of LGL/NK cells. Higher MF doses (1.0. 5.0 mg/kg) induced an early increase (up to 300 Delta% and 29 Delta%, respectively) followed by a decrease in cytotoxicity (to-76 Delta% after 5.0 mg/kg), and in LGL number (-36 Delta% after 5.0 mg/kg). These effects were concomitant with a marked rise in plasma COR (up to 234 Delta% after 0.5 mg/kg and 567 Delta% after 5.0 mg/kg of MF). NX pretreatment blocked all the changes in cytotoxicity but not in the LGL cell number and COR concentrations. The results indicate that MF, besides having well known immunosuppressive effects, can also enhance NKCC through the opioid receptors-dependent manner. The enhancement of cytotoxicity appears as a purely functional change independent of the recirculation of NK cells which occurs despite the high plasma concentrations of COR. (c) 2008 Elsevier B.V. All rights reserved.