Thomas P T, Bhargava H N, House R V
Life Sciences Department, University of Illinois at Chicago, USA.
Pharmacology. 1995 Jan;50(1):51-62. doi: 10.1159/000139266.
Both in vivo and in vitro exposure to morphine have been reported to produce a number of immunomodulatory effects in both laboratory animals and humans. The current study was performed to assess the direct in vitro effect of exposure to morphine or morphine metabolites on immune response parameters. Murine B6C3F1 splenic lymphocytes or peritoneal macrophages were cultured in vitro at concentrations of 0.0001-100 mumol/l morphine sulfate, morphine-3-glucuronide, morphine-6-glucuronide, or normorphine. B cell proliferation was significantly suppressed following exposure to all drugs. Production of interleukin (IL)-2, IL-4, and IL-6 was affected only moderately by all drugs except morphine-6-glucuronide, which produced a marked suppression at 100 mumol/l. Both basal and augmented natural killer (NK) cell function were unaffected by any drug except morphine-6-glucuronide, which enhanced NK cell activity at concentrations between 0.0001 and 1.0 mumol/l. In contrast, both morphine-3-glucuronide and morphine-6-glucuronide significantly inhibited cytotoxic T lymphocyte induction at concentrations between 0.0001 and 100 mumol/l, whereas morphine and normorphine were inactive in this assay. In summary, in the absence of direct cellular cytotoxicity, a differential immunomodulation was observed following in vitro exposure to morphine and its metabolites.
据报道，在实验室动物和人类中，体内和体外接触吗啡都会产生多种免疫调节作用。本研究旨在评估接触吗啡或吗啡代谢产物对免疫反应参数的直接体外作用。将小鼠B6C3F1脾淋巴细胞或腹腔巨噬细胞在体外培养，培养基中硫酸吗啡、吗啡 - 3 - 葡萄糖醛酸苷、吗啡 - 6 - 葡萄糖醛酸苷或去甲吗啡的浓度为0.0001 - 100 μmol/L。接触所有药物后，B细胞增殖均受到显著抑制。除吗啡 - 6 - 葡萄糖醛酸苷在100 μmol/L时产生明显抑制外，所有药物对白细胞介素（IL）-2、IL - 4和IL - 6的产生影响较小。除吗啡 - 6 - 葡萄糖醛酸苷在0.0001至1.0 μmol/L浓度范围内增强自然杀伤（NK）细胞活性外，任何药物对基础和增强的NK细胞功能均无影响。相反，吗啡 - 3 - 葡萄糖醛酸苷和吗啡 - 6 - 葡萄糖醛酸苷在0.0001至100 μmol/L浓度范围内均显著抑制细胞毒性T淋巴细胞的诱导，而吗啡和去甲吗啡在该实验中无活性。总之，在不存在直接细胞毒性的情况下，体外接触吗啡及其代谢产物后观察到了不同的免疫调节作用。
