Laboratory of the Biology of Tissue Healing, Ontogeny and Nutrition, Department of Morphology and Institute of Biomedicine, School of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo, 1315 Fortaleza, CE, Brazil.
Exp Biol Med (Maywood). 2014 Apr;239(4):442-53. doi: 10.1177/1535370213520114. Epub 2014 Feb 28.
Periodontitis is a chronic inflammatory disease related to tooth loss in adults. Infliximab is a chimeric monoclonal antibody against TNF-α and is prescribed for the treatment of systemic inflammatory diseases. This study aimed to investigate the role of infliximab on experimental periodontal disease (EPD). EPD was induced by passing a 3.0 nylon thread around the upper left second molar in Wistar rats. Animals were either treated with intravenous infliximab (1, 5, 7, and 10 mg/kg) or saline solution 30 min before the periodontitis induction and were followed until they were sacrificed on the 11th day. A subset of rats was euthanized on the third day for analysis of gingival myeloperoxidase (MPO) and the blood MPO granulocyte index. In addition, we analyzed the bone loss index (BLI), the periodontal histopathological score, and the periodontal collagen network using confocal microscopy. We also analyzed metalloproteinase-1/-8, RANK, RANK-L, and osteoprotegerin in maxillary tissue by immunohistochemistry Gingival MPO, IL-1β, TNF-α were measured by ELISA. EPD caused leukocytosis, significant increases in BLI and gingival pro-inflammatory cytokines and cell infiltrates, with worse histopathological scores and periodontal collagen derangement. Infliximab (5 mg/kg) reduced granulocyte blood counts, gingival IL-1β, TNF-α, and MPO levels, diminished MMP-1/-8, RANK, and RANK-L bone immunolabeling with better periodontal histopathological scores and collagen network in comparison with the challenged saline group. We concluded that infliximab had significant anti-inflammatory and bone-protective effects in Wistar rats challenged by periodontitis.
牙周炎是一种与成年人牙齿缺失有关的慢性炎症性疾病。英夫利昔单抗是一种针对 TNF-α 的嵌合单克隆抗体,用于治疗全身性炎症性疾病。本研究旨在探讨英夫利昔单抗在实验性牙周病(EPD)中的作用。通过在上颌左侧第二磨牙周围穿过 3.0 尼龙线诱导 EPD。动物在牙周炎诱导前 30 分钟分别接受静脉内英夫利昔单抗(1、5、7 和 10mg/kg)或生理盐水治疗,并在第 11 天处死时进行随访。一部分大鼠在第 3 天处死,用于分析牙龈髓过氧化物酶(MPO)和血液 MPO 粒细胞指数。此外,我们还使用共聚焦显微镜分析了骨损失指数(BLI)、牙周组织病理学评分和牙周胶原网络。我们还通过免疫组织化学分析了上颌组织中的基质金属蛋白酶-1/-8、RANK、RANK-L 和骨保护素,并用 ELISA 测量了牙龈 MPO、IL-1β 和 TNF-α。EPD 导致白细胞增多,BLI 和牙龈促炎细胞因子和细胞浸润显著增加,组织病理学评分和牙周胶原紊乱更差。与生理盐水组相比,英夫利昔单抗(5mg/kg)减少了粒细胞计数、牙龈 IL-1β、TNF-α 和 MPO 水平,降低了 MMP-1/-8、RANK 和 RANK-L 的骨免疫标记,牙周组织病理学评分和胶原网络得到改善。我们得出结论,英夫利昔单抗对牙周炎挑战的 Wistar 大鼠具有显著的抗炎和骨保护作用。