Department of Immunology School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Exp Parasitol. 2012 Jan;130(1):73-7. doi: 10.1016/j.exppara.2011.09.006. Epub 2011 Oct 12.
BALB/c mice are susceptible to develop non-healing, progressive infection with Leishmania major (L. major) due to the development of a non-protective Th2 response. Resistance to L. major infection is dependent to Th1 response. Treatment of mice with the opioid antagonist naloxone can promote the activation of Th1 responses. Here we study the effect of chronic administration of various doses of naloxone on susceptibility of BALB/c mice to L. major infection. Our results showed that naloxone has dose-dependent biphasic effect on L. major infection in BALB/c mice. While administration of 1mg/kg × 2/day tends to exacerbate the local reaction to L. major infection, treatment with 10mg/kg × 2/day of naloxone suppresses the local reaction and progress of infection. On the other hand treatment of mice with middle dose (5mg/kg whether 1 or 2 times per day) does not have significant effect on the infection. This study demonstrates that administration of high dose of naloxone could improve protection against L. major infection in BALB/c mice, presumably by modulation in Th1/Th2 balance or by affecting macrophages through binding to Toll-like receptors.
BALB/c 小鼠由于产生非保护性 Th2 反应而易发生无法治愈的、进行性利什曼原虫（L. major）感染。对 L. major 感染的抵抗力取决于 Th1 反应。用阿片受体拮抗剂纳洛酮治疗小鼠可以促进 Th1 反应的激活。在这里，我们研究了慢性给予不同剂量纳洛酮对 BALB/c 小鼠对 L. major 感染易感性的影响。我们的结果表明，纳洛酮对 BALB/c 小鼠的 L. major 感染具有剂量依赖性的双相作用。虽然给予 1mg/kg×2/天的纳洛酮倾向于加剧对 L. major 感染的局部反应，但给予 10mg/kg×2/天的纳洛酮抑制局部反应和感染的进展。另一方面，用中等剂量（5mg/kg，无论是每天 1 次还是 2 次）治疗小鼠对感染没有显著影响。这项研究表明，给予高剂量的纳洛酮可以改善 BALB/c 小鼠对 L. major 感染的保护作用，推测是通过调节 Th1/Th2 平衡或通过与 Toll 样受体结合影响巨噬细胞来实现的。
