Limiroli Elena, Gaspani Leda, Panerai Alberto E, Sacerdote Paola
Department of Pharmacology, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
J Leukoc Biol. 2002 Jul;72(1):43-8.
Morphine has been shown to affect cell-mediated and humoral immune parameters. In this study, we investigated the capacity of in vivo acute and chronic morphine treatment to modulate interleukin (IL)-10 and IL-12 production by LPS and interferon-gamma-stimulated resident and thioglycollate-elicited murine peritoneal macrophages and the development of tolerance to these effects. One hour after the acute administration of 5, 10, and 20 mg/Kg morphine, a dose-related decrease of IL-10 and IL-12 levels was present. The pretreatment with naltrexone at doses up to 20 mg/Kg did not prevent the decrease of IL-10 and IL-12 induced by morphine. When the drug was administered chronically, a differential development of tolerance to the immune effects was observed. After 3 days of treatment, the effect of the acute challenge with 20 mg/Kg morphine on IL-12 was lost. In contrast, morphine-induced inhibition of IL-10 disappeared between 10 and 12 days of treatment, in parallel with tolerance to the antinociceptive effect. These results suggest that morphine treatment affects macrophage cytokine production and that tolerance affects this modulation differently.
吗啡已被证明会影响细胞介导和体液免疫参数。在本研究中，我们调查了体内急性和慢性吗啡治疗对脂多糖（LPS）和γ-干扰素刺激的驻留及巯基乙酸盐诱导的小鼠腹腔巨噬细胞产生白细胞介素（IL）-10和IL-12的调节能力，以及对这些作用产生耐受性的情况。急性给予5、10和20mg/Kg吗啡1小时后，IL-10和IL-12水平出现剂量相关的下降。高达20mg/Kg剂量的纳曲酮预处理并不能阻止吗啡诱导的IL-10和IL-12水平下降。当长期给药时，观察到对免疫作用的耐受性出现差异发展。治疗3天后，20mg/Kg吗啡急性激发对IL-12的作用消失。相反，吗啡诱导的IL-10抑制在治疗10至12天之间消失，与对抗痛觉作用的耐受性同时出现。这些结果表明，吗啡治疗会影响巨噬细胞细胞因子的产生，且耐受性对这种调节的影响有所不同。
