Khalili Ahmad, Hassan Zuhair Muhammad, Shahabi Shahram, Pourfathollah Ali Akbar, Ostad Seyed Nasser, Noori Shokoofe, Mahdavi Mehdi, Haybar Habib, Langroudi Ladan
Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Iran J Immunol. 2013 Jun;10(2):70-82.
Noradrenaline (NA), the principal neurotransmitter released from sympathetic nerve terminals, influences T-cell maturation, not only directly in developing T cells, but also indirectly, by acting on the thymic nonlymphoid cells. In vitro and in vivo studies have demonstrated the anti-proliferative, anti-migratory, anti-angiogenic and cytotoxic properties of propranolol, β-AR blocker, against various cancers.
To evaluate the effect of propranolol on efficacy of HSP-70 rich lysate vaccine in immunotherapy of fibrosarcoma.
Mouse fibrosarcoma WEHI-164 cells were used to immunize tumor-bearing mice with or without propranolol and HSP-70. Splenocytes proliferation, cytotoxicity activity of the splenocytes, naturally occurring CD4+ CD25high T-reg cells and IFN-γ and IL-4 secretion as well as tumor size, were assessed to describe the anti-tumor immune response.
A significant increase in the level of IFN-γ in the mice vaccinated with WEHI-164 cells enriched with HSP-70 and co-treated with propranolol was observed compared to controls. However, HSP enrichment or propranolol treatment alone did not enhance the immune response as measured by the level of IFN-γ. Likewise, a decrease in tumor growth in the test group (p<0.01) and a significant increase in CTL activity (p<0.05) was observed.
HSP enriched vaccine shows anti-tumor activity, probably due to the modulation of immune responses.
去甲肾上腺素（NA）是交感神经末梢释放的主要神经递质，不仅直接影响发育中的T细胞成熟，还通过作用于胸腺非淋巴细胞间接影响T细胞成熟。体外和体内研究已证明β-肾上腺素能受体阻滞剂普萘洛尔对各种癌症具有抗增殖、抗迁移、抗血管生成和细胞毒性特性。
评估普萘洛尔对富含热休克蛋白70（HSP-70）的裂解物疫苗在纤维肉瘤免疫治疗中疗效的影响。
用小鼠纤维肉瘤WEHI-164细胞免疫荷瘤小鼠，同时给予或不给予普萘洛尔和HSP-70。评估脾细胞增殖、脾细胞的细胞毒性活性、天然存在的CD4+CD25高表达调节性T细胞以及干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）分泌以及肿瘤大小，以描述抗肿瘤免疫反应。
与对照组相比，观察到用富含HSP-70的WEHI-164细胞免疫并联合普萘洛尔治疗的小鼠中IFN-γ水平显著升高。然而，单独的HSP富集或普萘洛尔治疗并未如通过IFN-γ水平所测量的那样增强免疫反应。同样，在测试组中观察到肿瘤生长减少（p<0.01）和细胞毒性T淋巴细胞（CTL）活性显著增加（p<0.05）。
富含HSP的疫苗显示出抗肿瘤活性，可能是由于免疫反应的调节。
