*Division of Allergy and Immunology, Department of Pediatrics, Jaffe Food Allergy Institute; †Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics; and ‡Division of Clinical Immunology, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; and §Department of Pathology, Columbia University Medical School, New York, New York.
Inflamm Bowel Dis. 2014 Jan;20(1):144-53. doi: 10.1097/01.MIB.0000436467.37566.48.
Crohn's disease (CD) is a chronic inflammatory disease with increasing incidence in children. Current medications have potentially serious side effects, hence increasing interest in alternative therapies. We previously developed an herbal formula, FAHF-2, based on a classical traditional Chinese herbal formula Wu Mei Wan that has long been used in China to treat colitis. We investigated FAHF-2's potential anti-inflammatory effects.
FAHF-2 efficacy was tested in vivo in the CD45RbRAG1 transfer colitis model. Weight loss, colonic histology, and cytokine production from mesenteric lymph nodes were assessed. Human peripheral blood mononuclear cells (PBMCs) and colonic biopsies were obtained from children newly diagnosed with CD and controls and cultured with or without FAHF-2. Cytokine levels were measured by multiplex immunoassay. The effect of FAHF-2 on TNF-α-producing cells was determined by flow cytometry. NF-κB signaling was investigated in human lamina propria mononuclear cells upon FAHF-2 treatment by In-Cell Western.
FAHF-2-treated mice had decreased weight loss, improved histology, and reduced TNF-α, IL-17, IL-6, and IFN-γ production. In vitro treated PBMCs produced less TNF-α, IFN-γ, and IL-12. FAHF-2 reduced the TNF-α-producing monocytes and T cells. Inflamed CD biopsies produced less TNF-α, IL-17, IL-6, and IL-1β. These effects are because of decreased NF-κB activation.
FAHF-2 inhibited both adaptive and innate immune proinflammatory cytokine responses in PBMCs and inflamed CD mucosa due in part to blockage of NF-κB activation. FAHF-2 was effective in halting progression of colitis in a murine model. This study shows that FAHF-2 has potential as a novel treatment of CD.
克罗恩病(CD)是一种慢性炎症性疾病,其在儿童中的发病率呈上升趋势。目前的药物可能有严重的副作用,因此人们对替代疗法的兴趣日益增加。我们之前根据一种经典的中药方剂乌梅丸开发了一种草药配方 FAHF-2,该方剂在中国长期用于治疗结肠炎。我们研究了 FAHF-2 的潜在抗炎作用。
在 CD45RbRAG1 转移结肠炎模型中体内测试 FAHF-2 的疗效。评估体重减轻、结肠组织学和肠系膜淋巴结细胞因子的产生。从新诊断为 CD 的儿童和对照中获得人外周血单核细胞(PBMC)和结肠活检,并在有或没有 FAHF-2 的情况下培养。通过多重免疫测定法测量细胞因子水平。通过流式细胞术确定 FAHF-2 对 TNF-α 产生细胞的影响。通过 In-Cell Western 研究 FAHF-2 处理后人固有层单核细胞中的 NF-κB 信号。
用 FAHF-2 治疗的小鼠体重减轻减少,组织学改善,TNF-α、IL-17、IL-6 和 IFN-γ产生减少。体外处理的 PBMC 产生的 TNF-α、IFN-γ和 IL-12 减少。FAHF-2 减少了 TNF-α 产生的单核细胞和 T 细胞。发炎的 CD 活检产生的 TNF-α、IL-17、IL-6 和 IL-1β 减少。这些作用是由于 NF-κB 激活减少。
FAHF-2 抑制了 PBMC 中适应性和固有免疫促炎细胞因子反应以及发炎的 CD 黏膜,部分原因是阻断了 NF-κB 激活。FAHF-2 可有效阻止结肠炎在小鼠模型中的进展。这项研究表明 FAHF-2 具有作为 CD 新型治疗方法的潜力。