Carpenter G W, Garza H H, Gebhardt B M, Carr D J
Department of Microbiology, Louisiana State University Medical Center, New Orleans 70112-1393.
Brain Behav Immun. 1994 Sep;8(3):185-203. doi: 10.1006/brbi.1994.1018.
Exposure to opioid drugs (e.g., morphine) in vivo has been shown to suppress natural killer cell activity. However, the effects of in vivo exposure to opioids on cytotoxic T lymphocyte (CTL) activity has not been investigated. The administration of morphine (50.0 mg/kg, sc) to alloimmunized mice for 11 days resulted in a significant decrease in peritoneal and splenic CTL activity. Moreover, the intracellular content of serine esterases and esterase release by CD8+ effector cells from chronic morphine-treated mice was reduced compared to that of effector cells from vehicle-treated controls. In addition, the CD8+ cAMP response to alloantigen was diminished compared to CD(8+)-enriched cells from vehicle-treated animals. However, conjugate formation between effector and target and subsequent killing of target by effector cells did not reveal significant differences between vehicle- and chronic morphine-treated animals. Serum corticosterone and dehydroepiandrosterone levels were significantly lower in the chronic morphine-treated animals while proopiomelanocortin gene expression (exon 3) in splenic lymphocytes did not correlate with morphine-mediated suppression of CTL activity. These results indicate that CTL activity is sensitive to chronic morphine exposure, implicating opioids as important cofactors during viral infections in suppressing cell-mediated immunity.
体内暴露于阿片类药物(如吗啡)已被证明会抑制自然杀伤细胞的活性。然而,体内暴露于阿片类药物对细胞毒性T淋巴细胞(CTL)活性的影响尚未得到研究。给同种免疫小鼠皮下注射吗啡(50.0 mg/kg),持续11天,导致腹膜和脾脏CTL活性显著降低。此外,与接受溶剂处理的对照组效应细胞相比,慢性吗啡处理小鼠的CD8 +效应细胞中丝氨酸酯酶的细胞内含量和酯酶释放量减少。另外,与接受溶剂处理动物的CD8 +细胞相比,慢性吗啡处理小鼠的CD8 +细胞对同种抗原的cAMP反应减弱。然而,效应细胞与靶细胞之间的结合形成以及随后效应细胞对靶细胞的杀伤在接受溶剂处理和慢性吗啡处理的动物之间未显示出显著差异。慢性吗啡处理动物的血清皮质酮和脱氢表雄酮水平显著较低而脾脏淋巴细胞中阿片促黑皮质素原基因表达(外显子3)与吗啡介导的CTL活性抑制无关。这些结果表明CTL活性对慢性吗啡暴露敏感,提示阿片类药物在病毒感染期间作为抑制细胞介导免疫的重要辅助因子。