Ben-Ami Shor Dana, Lachnish Jordan, Bashi Tomer, Dahan Shani, Shemer Asaf, Segal Yahel, Shovman Ora, Halpert Gilad, Volkov Alexander, Barshack Iris, Amital Howard, Blank Miri, Shoenfeld Yehuda
Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center Tel-Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 52620, Israel.
Department of Gastroenterology, Tel-Aviv Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6423906, Israel.
J Clin Med. 2019 Dec 26;9(1):65. doi: 10.3390/jcm9010065.
Helminths or their products can immunomodulate the host immune system, and this phenomenon may be applied as the basis of new anti-inflammatory treatments. Previously, we have shown the efficacy of tuftsin-phosphorylcholine (TPC), based on a helminth product, in four animal models of autoimmune diseases: arthritis, colitis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis. We demonstrated that TPC reduced inflammatory process ex vivo in peripheral blood lymphocytes (PBLs) and in biopsies from giant-cell arteritis. In the present study, we assessed the therapeutic potential of TPC treatment on a chronic colitis murine model. C57BL/6 mice with chronic colitis were treated with TPC after the third cycle of 2% dextran sodium sulfate (DSS). Oral TPC treatment resulted in amelioration of the colitis clinical manifestations exemplified by reduced disease activity index (DAI) score, expansion of mesenteric lymph nodes (MLN) T regulatory cells (shown by Fluorescence Activated Cell Sorting (FACS)), significant reduction in the expression of pro-inflammatory cytokines (IL-1β, IL17, IL-6, TNFα), and elevation in the expression of anti-inflammatory cytokine IL-10 (shown by RT-PCR). This study demonstrated the potential immunomodulatory effects of oral administration of TPC in a chronic colitis murine model. Further clinical trials are needed in order to evaluate this novel approach for the treatment of patients with inflammatory bowel disease.
蠕虫或其产物可调节宿主免疫系统，这一现象可作为新型抗炎治疗的基础。此前，我们已证明基于蠕虫产物的促吞噬肽-磷酰胆碱（TPC）在四种自身免疫性疾病动物模型中具有疗效：关节炎、结肠炎、系统性红斑狼疮和实验性自身免疫性脑脊髓炎。我们证明TPC在体外可减轻外周血淋巴细胞（PBL）以及巨细胞动脉炎活检组织中的炎症过程。在本研究中，我们评估了TPC治疗对慢性结肠炎小鼠模型的治疗潜力。在2%葡聚糖硫酸钠（DSS）的第三个周期后，用TPC治疗患有慢性结肠炎的C57BL/6小鼠。口服TPC治疗可改善结肠炎的临床表现，表现为疾病活动指数（DAI）评分降低、肠系膜淋巴结（MLN）调节性T细胞增多（通过荧光激活细胞分选（FACS）显示）、促炎细胞因子（IL-1β、IL-17、IL-6、TNFα）表达显著降低以及抗炎细胞因子IL-10表达升高（通过逆转录-聚合酶链反应（RT-PCR）显示）。本研究证明了口服TPC在慢性结肠炎小鼠模型中的潜在免疫调节作用。为了评估这种治疗炎症性肠病患者的新方法，还需要进一步的临床试验。
