Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Manipal Centre for Virus Research, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Scand J Immunol. 2019 Apr;89(4):e12749. doi: 10.1111/sji.12749. Epub 2019 Mar 5.
Chitosan, the deacetylated form of chitin, a natural polysaccharide, is known for its various biomedical applications. The present study aimed at exploring the immunomodulatory properties of chitosan (CSNP) and gallic acid-grafted chitosan (cGANP) nanoparticles in mice model of cyclophosphamide (CPA)-induced immunosuppression. In addition, chitooligosaccharides, the hydrolysed form of chitin and chitosan, were also evaluated for its potential against immunosuppression in mice. CPA (80 mg/kg/ip) induced significant immunosuppression, which was reversed with cGANP treatment as indicated by a significant increase in the thymus and spleen indices compared to the CPA-treated group. The CSNP and chitooligosaccharides (chitin and chitosan) failed to reverse CPA-induced changes. ELISA revealed an elevation in the levels of IL-6 and a reduction in IFN-γ levels with CPA treatment. All the test compounds reduced the IL-6 levels, whereas only the nanoparticle formulations (CSNP and cGANP) exhibited a significant augmentation in the IFN-γ levels. Both the cytokines, IL-6 and IFN-γ, are secreted separately by two different types of T helper cells (Th cells), which mediate cellular and humoral immune responses in a coordinated manner. Th-1 cells release IFN-γ, facilitating cell-mediated immunity, whereas IL-6 is released by Th-2 cells, expediting humoral immune response. The nanoparticles (CSNP and cGANP) seemed to be better immune enhancers than the chitooligosaccharides owing to their ability to reverse the cytokine changes induced by CPA. Overall, it was evident that the nanoparticles, most likely, boosted the cell-mediated immunity through the induction of the Th-1 branch of the immune response.
壳聚糖是甲壳素的去乙酰化形式，是一种天然多糖，具有多种生物医学应用。本研究旨在探索壳聚糖（CSNP）和没食子酸接枝壳聚糖（cGANP）纳米粒子在环磷酰胺（CPA）诱导免疫抑制的小鼠模型中的免疫调节特性。此外，还评估了壳寡糖，即甲壳素和壳聚糖的水解形式，其对小鼠免疫抑制的潜在作用。CPA（80mg/kg/ip）诱导明显的免疫抑制，与 cGANP 治疗相比，脾和胸腺指数显著增加，表明免疫抑制得到逆转。CSNP 和壳寡糖（壳聚糖和壳聚糖）未能逆转 CPA 诱导的变化。ELISA 显示，与 CPA 处理组相比，IL-6 水平升高，IFN-γ 水平降低。所有测试化合物均降低了 IL-6 水平，而只有纳米粒子制剂（CSNP 和 cGANP）显示 IFN-γ 水平显著升高。这两种细胞因子，IL-6 和 IFN-γ，分别由两种不同类型的辅助性 T 细胞（Th 细胞）分泌，它们以协调的方式介导细胞和体液免疫反应。Th1 细胞释放 IFN-γ，促进细胞介导的免疫，而 IL-6 则由 Th2 细胞释放，加速体液免疫反应。纳米粒子（CSNP 和 cGANP）似乎比壳寡糖更好的免疫增强剂，因为它们能够逆转 CPA 诱导的细胞因子变化。总的来说，很明显，纳米粒子很可能通过诱导免疫反应的 Th1 分支来增强细胞介导的免疫。
