Kim Kyung-Jin, Park Jun-Bean, Lee Seung-Pyo, Kim Hyung-Kwan, Kim Yong-Jin
Department of Internal Medicine, Ewha Womans University Medical Center, Ewha Womans University School of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Korean Circ J. 2023 Dec;53(12):795-810. doi: 10.4070/kcj.2023.0042. Epub 2023 Aug 28.
Myocarditis is a potentially fatal disease, but curative treatments have not yet been established. Myocardial inflammation is an important pathogenesis of this disease, and immunosuppressants such as methylprednisolone and immunoglobulin have been used for treatment; however, the effectiveness needs to be improved. Thalidomide and dipeptidyl peptidase (DPP) 4 inhibitors were recently investigated regarding their immunomodulatory properties. This study aimed to test whether thalidomide or a DPP4 inhibitor (evogliptin) can improve the effectiveness of myocarditis treatment using a rat model of experimental autoimmune myocarditis (EAM).
Rats with or without myocarditis were administered thalidomide at 100 mg/kg/day and DPP4 inhibitor at 10 mg/kg/day orally. Measurement of echocardiography, serum inflammatory cytokines, myocardial histopathological examination, and immunohistochemical staining for leukocytes, macrophages, CD4+ T cells, and cytoskeleton were performed after 3 weeks, and the fibrosis area was measured after 3 and 6 weeks.
Thalidomide and DPP4 inhibitor did not reduce the severity of myocarditis compared with the EAM without treatment rats by comparing the echocardiographic data, myocardial CD4, macrophages, neutrophil infiltrations, and the heart weight/body weight ratio in 3 weeks. The levels of inflammatory cytokines were not lower in the thalidomide and DPP4 inhibitor-treated group than in the untreated group in 3 weeks. In 6 weeks, thalidomide and DPP4 inhibitors did not reduce the fibrosis area compared to untreated groups.
Although thalidomide and the DPP4 inhibitor had an immunomodulatory effect and are used against inflammatory diseases, they did not ameliorate myocardial inflammation and fibrosis in this rat model of EAM.
心肌炎是一种潜在的致命疾病，但尚未确立治愈性治疗方法。心肌炎症是该疾病的重要发病机制，已使用甲基泼尼松龙和免疫球蛋白等免疫抑制剂进行治疗；然而，其有效性仍有待提高。沙利度胺和二肽基肽酶（DPP）4抑制剂最近因其免疫调节特性而受到研究。本研究旨在使用实验性自身免疫性心肌炎（EAM）大鼠模型，测试沙利度胺或DPP4抑制剂（依格列净）是否能提高心肌炎治疗的有效性。
对患有或未患有心肌炎的大鼠口服给予沙利度胺，剂量为100mg/kg/天，给予DPP4抑制剂，剂量为10mg/kg/天。3周后进行超声心动图测量、血清炎症细胞因子检测、心肌组织病理学检查以及白细胞、巨噬细胞、CD4 + T细胞和细胞骨架的免疫组化染色，并在3周和6周后测量纤维化面积。
通过比较3周时的超声心动图数据、心肌CD4、巨噬细胞、中性粒细胞浸润以及心脏重量/体重比，与未治疗的EAM大鼠相比，沙利度胺和DPP4抑制剂并未降低心肌炎的严重程度。3周时，沙利度胺和DPP4抑制剂治疗组的炎症细胞因子水平并不低于未治疗组。在6周时，与未治疗组相比，沙利度胺和DPP4抑制剂并未减少纤维化面积。
尽管沙利度胺和DPP4抑制剂具有免疫调节作用，且用于治疗炎症性疾病，但在该EAM大鼠模型中，它们并未改善心肌炎症和纤维化。
