Evaluation of the effects of specific inhibition of IL6R on ligature-induced Periodontitis in rats with experimental Rheumatoid Arthritis

• Grant number: 21/02523-7
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2021
• End date: February 28, 2027
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Mario Taba Junior
• Grantee: Ana Carolina Aparecida Rivas
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 23/03753-1 - Porphyromonas gingivalis peptidylarginine deiminase (PPAD): biochemical evaluation of a novel link for breaching immunologic tolerance in rheumatoid arthritis, BE.EP.DD

Abstract

Periodontal Disease (PD), Rheumatoid Arthritis (RA) are immunoinflammatory diseases characterized by bone resorption induced by the inflammatory process (Mercado F, et al, 2000; Preshaw PM, 2017). Although these diseases have different etiological factors, they all share similar risk factors and pathogenic mechanisms (Preshaw PM, 2017; Potempa J, et al 2017; Redman RS, et al 2016). Although the exact etiology of RA remains unknown to date, the production of pro-inflammatory cytokines and activation of lymphocytes are crucial in the events of the disease, as well as in Periodontal Disease (de Aquino, SG et al., 2014; Lubberts, E 2010; Lundy, SK, et al., 2007).Thus, within the new therapeutic strategies, the modulation of the host's immune response seems to have great potential. Interleukin 6 (IL-6) is a potent stimulator of osteoclast differentiation and bone resorption. Excessive amounts of IL-6 are produced orally in patients with Periodontitis. Tocilizumab, formerly known as Myeloma Receptor Antibody (MRA), is a humanized IL-6 receptor monoclonal antibody that inhibits the dimerization of the IL-6/IL-6R complex, preventing signaling. Thus, taking into account advances in the pathogenesis of periodontal disease, their interactions with systemic diseases and new techniques for modulating the host's inflammatory response, this study aims to evaluate the role of the IL6 receptor antibody in rats with RA induced and exposed to ligature-induced Periodontal Disease. 60 winstar hannover rats will be used, divided into 6 groups (n = 10): Naive group (negative control); DP group (ligature-induced Periodontal Disease), AR group (bovine collagen-induced rheumatoid arthritis, AR/DP group (AR induced by bovine collagen and PD), AR-Sham/DP group (Sham Procedure in place of ligation-induced RA and DP); AR/DP/TCZ4 group (bovine collagen-induced RA and PD, but which will receive 4mg/kg of tocilizumab). The animals will be euthanized on the 28th day. The outcomes will be evaluated through histometric, histochemical, micro-tomographic, gene expression (PCR array) and immunoenzymatic analyzes. (AU)