State Key Laboratories of Agro-biotechnology, College of Biological Science, China Agricultural University, Beijing 100094, China.
Vaccine. 2011 Jun 24;29(29-30):4862-8. doi: 10.1016/j.vaccine.2011.03.091. Epub 2011 Apr 8.
Cimetidine (CIM) is a histamine H2 receptor inverse agonist used primarily as an anti-stomach acids drug, but recent studies showed that it may also modulate immune responses. To evaluate its potential usefulness as an adjuvant, we determined its immune modulating effects on subunit immunization using an HBV-derived recombinant protein antigen rHBsAg. CIM activated the PI3K-Akt signaling pathway in DCs. As an adjuvant, it activated immunogenic DCs, deactivated tolerogenic T cells (nTreg), and augmented both Th1- and Th2-polarlized immune responses to rHBsAg. As a result, it enhanced both antibody- and cytotoxic T cell-mediated immune responses. Importantly, in comparison with the FDA-approved human adjuvant alum, CIM is superior in its ability to block IL-10 up-regulation and potentiate Th1/Th2 dual polarization. These results suggest that CIM may be a better adjuvant for therapeutic vaccines against chronic viral infection, such as the HBV infection, where dual polarization should allow more effective elimination of infected host cells.
西咪替丁（CIM）是一种组胺 H2 受体反向激动剂，主要用作抗胃酸药物，但最近的研究表明，它还可能调节免疫反应。为了评估其作为佐剂的潜在用途，我们使用 HBV 衍生的重组蛋白抗原 rHBsAg 确定了其对亚单位免疫的免疫调节作用。CIM 在 DC 中激活了 PI3K-Akt 信号通路。作为佐剂，它激活了免疫原性 DC，使耐受性 T 细胞（nTreg）失活，并增强了 rHBsAg 的 Th1 和 Th2 极化免疫反应。结果，它增强了抗体和细胞毒性 T 细胞介导的免疫反应。重要的是，与 FDA 批准的人类佐剂明矾相比，CIM 阻断 IL-10 上调和增强 Th1/Th2 双重极化的能力更强。这些结果表明，CIM 可能是治疗慢性病毒感染（如 HBV 感染）的疫苗的更好佐剂，双重极化应允许更有效地清除感染的宿主细胞。
