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Orally administered anti-eotaxin-1 monoclonal antibody is biologically active in the gut and alleviates immune-mediated hepatitis: A novel anti-inflammatory personalized therapeutic approach
International Journal of Immunopathology and Pharmacology ( IF 3.0 ) Pub Date : 2021-07-17 , DOI: 10.1177/20587384211021215
Tawfik Khoury 1 , Dory Rotnemer-Golinkin 1 , Lidya Zolotarev 1 , Yaron Ilan 1
Affiliation  

Personalized therapies are designed to optimize the safety-to-efficacy ratio by selecting patients with higher response rates based on specific biomarkers. Inflammation plays a vital role in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common liver disorder. Eotaxin-1 plays a role in innate and adaptive immune responses. High eotaxin-1 levels are associated with diabetes and fatty liver disease and, therefore, serves as a biomarker for patient selection. The anti-eotaxin-1 monoclonal antibody is tailored for the personalized therapy of patients with inflammatory conditions due to high levels of eotaxin-1. To evaluate the biological activity and immunomodulatory effect of orally administered anti-eotaxin-1. C57B1/6 mice were treated with either oral or intra-peritoneal anti-eotaxin-1 antibody before induction of immune-mediated hepatitis using an injection of concanavalin A (ConA) and checked for liver injury and eotaxin-1 serum levels. Oral administration of anti-eotaxin-1 alleviated the immune-mediated liver injury. Serum alanine aminotransferase levels decreased to 1807 U/L, compared with 19025 U/L in untreated controls and 3657 U/L in mice treated with parenteral anti-eotaxin-1 (P < 0.005). A trend toward reduced serum eotaxin-1 levels was observed in treated mice, ranging from 594 pg/mL in the controls to 554 and 561 pg/mL in mice treated orally and intraperitoneally (P = 0.08, P = 0.06, respectively). Oral administration of anti-eotaxin-1 antibody shows biological activity in the gut and exerts a systemic immunomodulatory effect to alleviate immune-mediated hepatitis. The data suggest that testing for eotaxin-1 serum levels may enable screening patients with high-eotaxin-1 levels-associated NASH.



中文翻译:

口服抗 eotaxin-1 单克隆抗体在肠道中具有生物活性,可缓解免疫介导的肝炎:一种新型的抗炎个性化治疗方法

个性化疗法旨在通过基于特定生物标志物选择具有较高反应率的患者来优化安全性与疗效比。炎症在非酒精性脂肪性肝炎 (NASH) 的发病机制中起着至关重要的作用,这是一种常见的肝脏疾病。Eotaxin-1 在先天性和适应性免疫反应中发挥作用。高 eotaxin-1 水平与糖尿病和脂肪肝疾病相关,因此可作为患者选择的生物标志物。抗 eotaxin-1 单克隆抗体专为因高水平 eotaxin-1 引起的炎症性疾病患者的个性化治疗而量身定制。评价口服抗-eotaxin-1的生物活性和免疫调节作用。在使用刀豆球蛋白 A (ConA) 注射诱导免疫介导的肝炎之前,C57B1/6 小鼠接受口服或腹腔内抗 eotaxin-1 抗体治疗,并检查肝损伤和 eotaxin-1 血清水平。口服抗 eotaxin-1 可减轻免疫介导的肝损伤。血清丙氨酸氨基转移酶水平降至 1807 U/L,而未治疗对照组为 19025 U/L,而接受肠外抗 eotaxin-1 治疗的小鼠为 3657 U/L。P < 0.005)。在接受治疗的小鼠中观察到血清 eotaxin-1 水平降低的趋势,范围从对照组的 594 pg/mL 到口服和腹膜内治疗的小鼠的 554 和 561 pg/mL(分别为P = 0.08,P = 0.06)。口服抗 eotaxin-1 抗体在肠道中显示出生物活性,并发挥全身免疫调节作用以减轻免疫介导的肝炎。数据表明,检测 eotaxin-1 血清水平可能有助于筛查患有高 eotaxin-1 水平相关 NASH 的患者。

更新日期:2021-07-18
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