Yacoub Tania, Rima Mohamad, Sadek Riyad, Hleihel Walid, Fajloun Ziad, Karam Marc
Department of Biology, University of Balamand, Kourah, Lebanon.
Sorbonne Universités, Department of Neuroscience, Institute of Biology Paris-Seine, CNRS UMR 8246, INSERM U1130, F-75005 Paris, France.
Toxicol Rep. 2018 Mar 1;5:318-323. doi: 10.1016/j.toxrep.2018.02.011. eCollection 2018.
Beside their toxicity, snake venom components possess several pharmacological effects and have been used to design many drugs. Recently, the cytotoxic, antibacterial, vasorelaxant, pro- and anti-coagulant as well as inflammatory activities of venom have been described . However, the effects of this Lebanese snake venom on the immune system has not been established yet. Here, we investigate the immunomodulatory effects of venom on the murine splenic levels of TNF-α, IFN-γ, IL-4, IL-10, IL-1ß and IL-17 at 6 and 24 h post treatment. Different doses of the venom (1 mg/kg, 2 mg/kg, 4 mg/kg and 6 mg/kg) were injected intraperitoneally in BALB/c mice. Using the logit method, LD of was proved to be 1.92 mg/kg in our experimental conditions. This study also shows that 1 mg/kg and 2 mg/kg of venom are able to modulate the levels of cytokines in the spleen of mice, as assessed by ELISA. In fact, this snake's venom up-regulates TNF-α, IFN-γ, IL-1ß and IL-17 with a trend in decreasing IL-4 and IL-10. Therefore, by favoring Th1 and Th17 over Th2 and Treg responses, venom might have important clinical implication especially in the field of cancer immunotherapy.
除了具有毒性外,蛇毒成分还具有多种药理作用,并已被用于设计多种药物。最近,人们描述了蛇毒的细胞毒性、抗菌、血管舒张、促凝血和抗凝血以及炎症活性。然而,这种黎巴嫩蛇毒对免疫系统的影响尚未确定。在此,我们研究了蛇毒在治疗后6小时和24小时对小鼠脾脏中肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、白细胞介素-1β(IL-1ß)和白细胞介素-17(IL-17)水平的免疫调节作用。将不同剂量的蛇毒(1毫克/千克、2毫克/千克、4毫克/千克和6毫克/千克)腹腔注射到BALB/c小鼠体内。在我们的实验条件下,使用对数单位法证明蛇毒的半数致死量为1.92毫克/千克。本研究还表明,通过酶联免疫吸附测定法(ELISA)评估,1毫克/千克和2毫克/千克的蛇毒能够调节小鼠脾脏中的细胞因子水平。事实上,这种蛇毒上调了TNF-α、IFN-γ、IL-1ß和IL-17,并呈现出降低IL-4和IL-10的趋势。因此,通过促进Th1和Th17反应而非Th2和调节性T细胞(Treg)反应,蛇毒可能具有重要的临床意义,特别是在癌症免疫治疗领域。