Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan.
BMC Complement Altern Med. 2011 Feb 4;11:9. doi: 10.1186/1472-6882-11-9.
Cytokines play a key role in the immune response to developing tumors, and therefore modulating their levels and actions provides innovative strategies for enhancing the activity of antigen presenting cells and polarizing towards T helper 1 type response within tumor microenvironment. One of these approaches could be the employment of plant extracts that have cytokine immunomodulation capabilities. Previously, we have shown that the Eriobotrya japonica hydrophilic extract (EJHE) induces proinflammatory cytokines in vitro and in vivo.
The present study explored the in vivo immunomodulatory effect on interferon-gamma (IFN-γ), interleukin-17 (IL-17), and transforming growth factor-beta 1 (TGF-β1) evoked by two water-extracts prepared from EJ leaves in the tissues of normal and Meth-A-fibrosarcoma bearing mice.
Intraperitoneal (i.p.) administration of 10 μg of EJHE and EJHE-water residue (WR), prepared from butanol extraction, increased significantly IFN-γ production in the spleen (p < 0.01) and lung (p < 0.03) tissues at 6-48 hours and suppressed significantly TGF-β1 production levels (p < 0.001) in the spleen for as long as 48 hours. The latter responses, however, were not seen in Meth-A fibrosarcoma-bearing mice. On the contrary, triple i.p. injections, 24 hours apart; of 10 μg EJHE increased significantly IFN-γ production in the spleen (p < 0.02) while only EJHE-WR increased significantly IFN-γ, TGF-β1 and IL-17 (p < 0.03 - 0.005) production within the tumor microenvironment of Meth-A fibrosarcoma. In addition, the present work revealed a significant prolongation of survival time (median survival time 72 days vs. 27 days of control, p < 0.007) of mice inoculated i.p. with Meth-A cells followed by three times/week for eight weeks of i.p. administration of EJHE-WR. The latter prolonged survival effect was not seen with EJHE.
The therapeutic value of EJHE-WR as an anticancer agent merits further investigation of understanding the effect of immunomodulators' constituents on the cellular components of the tissue microenvironment. This can lead to the development of improved strategies for cancer treatment and thus opening up a new frontier for future studies.
细胞因子在肿瘤发生过程中的免疫反应中发挥关键作用，因此调节其水平和作用为增强抗原呈递细胞的活性和在肿瘤微环境中向 T 辅助 1 型反应的极化提供了创新策略。其中一种方法可以是使用具有细胞因子免疫调节能力的植物提取物。先前，我们已经表明，水培日本梨（Eriobotrya japonica）亲水提取物（EJHE）在体外和体内诱导前炎性细胞因子。
本研究探讨了两种从 EJ 叶制备的水提取物对正常和 Meth-A 纤维肉瘤荷瘤小鼠组织中干扰素-γ（IFN-γ）、白细胞介素-17（IL-17）和转化生长因子-β1（TGF-β1）的体内免疫调节作用。
腹腔内（i.p.）给予 10μg EJHE 和 EJHE-水残渣（WR），由丁醇提取，可显著增加脾（p<0.01）和肺（p<0.03）组织中 IFN-γ的产生，并在 48 小时内显著抑制脾中 TGF-β1 的产生水平（p<0.001）。然而，在 Meth-A 纤维肉瘤荷瘤小鼠中未见后一种反应。相反，三次腹腔注射，间隔 24 小时；10μg EJHE 可显著增加脾中 IFN-γ的产生（p<0.02），而只有 EJHE-WR 可显著增加肿瘤微环境中的 IFN-γ、TGF-β1 和 IL-17（p<0.03-0.005）的产生。此外，本研究表明，腹腔接种 Meth-A 细胞后，每周三次腹腔注射 EJHE-WR 八周，可显著延长接种小鼠的存活时间（中位存活时间 72 天与对照组 27 天，p<0.007）。未观察到 EJHE 有延长存活时间的作用。
EJHE-WR 作为一种抗癌药物的治疗价值值得进一步研究，以了解免疫调节剂成分对组织微环境细胞成分的影响。这可以为癌症治疗的改进策略的发展提供依据，从而为未来的研究开辟新的前沿。
