title: Infliximab attenuates inflammatory osteolysis in a model of periodontitis in Wistar rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Davi C
authors.initials: DC
authors.lastname: Gonçalves
authors.forename: Rakel C
authors.initials: RC
authors.lastname: Evangelista
authors.forename: Rafael R
authors.initials: RR
authors.lastname: da Silva
authors.forename: Maria J S
authors.initials: MJ
authors.lastname: Santos
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Silva
authors.forename: Karoline S
authors.initials: KS
authors.lastname: Aragão
authors.forename: Gerly A C
authors.initials: GA
authors.lastname: Brito
authors.forename: Herene B M
authors.initials: HB
authors.lastname: Lucena
authors.forename: Renata C
authors.initials: RC
authors.lastname: Leitão
authors.forename: Reinaldo B
authors.initials: RB
authors.lastname: Oriá
mesh_terms: D016301:Alveolar Bone Loss; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017364:Collagenases / Q000378:metabolism; D007150:Immunohistochemistry; D000069285:Infliximab; D053583:Interleukin-1beta / Q000378:metabolism; D010014:Osteolysis / Q000188:drug therapy* / Q000473:pathology; D010518:Periodontitis / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D009195:Peroxidase; D017364:Collagenases
keywords: Infliximab; RANK; TNF-alpha; inflammation; periodontitis