Pohanka Miroslav, Pavlis Oto, Pikula Jiri
University of Defence, Trebesska, Hradec Kralove, Czech Republic.
Centre of Biological Defence, 56166 Techonin, Czech Republic.
Iran Biomed J. 2012;16(3):156-61. doi: 10.6091/ibj.993.2012.
Galantamine is a drug used for the treatment of Alzheimer's disease and some other cognitive disorders. It is an inhibitor of acetylcholinesterase; however, interaction with nicotinic acetylcholine receptors has also been reported. Owing to the significant role of cholinergic anti-inflammatory pathways in neuro-immunomodulation, we decided to examine the effect of galantamine on tularemia-infected BALB/c mice.
Animals were infected with Francisella tularensis LVS and treated with galantamine (0.1 mg/kg of body weight). Total mortality over the course of tularemia infection was assessed and interleukin 6 (IL-6) and interferon gamma (IFN-gamma) in plasma samples were measured by enzyme-linked immunosorbent assays. Apart from the cytokine assays, biochemical markers such as inorganic phosphate, uric acid, lactate dehydrogenase, gamma glutamyltransferase, creatinine phosphokinase and amylase were assayed.
The modulation of immunity by galantamine depended on two opposing processes: up-regulation of IFN-gamma and down-regulation of IL-6. Tularemia infection resulted in significant nephropathy, as hyperphosphataemia and hyperuricaemia occurred in infected animals. In addition, galantamine resulted in the mitigation of nephropathy, and markers of kidney dysfunction were modulated. Alterations in mortality were also found in this study.
Galantamine can significantly influence the immune response via the cholinergic anti-inflammatory pathway. Despite the decrease in IL-6 levels, galantamine treatment enhanced protection against the intracellular pathogen F. tularensis, resulting in the remission of some pathology and reduced mortality.
加兰他敏是一种用于治疗阿尔茨海默病和其他一些认知障碍的药物。它是一种乙酰胆碱酯酶抑制剂；然而，也有报道称其与烟碱型乙酰胆碱受体相互作用。由于胆碱能抗炎途径在神经免疫调节中具有重要作用，我们决定研究加兰他敏对兔热病感染的BALB/c小鼠的影响。
动物感染土拉弗朗西斯菌LVS并用加兰他敏（0.1mg/kg体重）治疗。评估兔热病感染过程中的总死亡率，并通过酶联免疫吸附测定法测量血浆样本中的白细胞介素6（IL-6）和干扰素γ（IFN-γ）。除了细胞因子测定外，还测定了无机磷酸盐、尿酸、乳酸脱氢酶、γ-谷氨酰转移酶、肌酸磷酸激酶和淀粉酶等生化标志物。
加兰他敏对免疫的调节取决于两个相反的过程：IFN-γ的上调和IL-6的下调。兔热病感染导致明显的肾病，因为感染动物出现高磷血症和高尿酸血症。此外，加兰他敏减轻了肾病，并调节了肾功能障碍标志物。本研究还发现死亡率有变化。
加兰他敏可通过胆碱能抗炎途径显著影响免疫反应。尽管IL-6水平降低，但加兰他敏治疗增强了对细胞内病原体土拉弗朗西斯菌的保护作用，导致一些病理状况缓解并降低了死亡率。
