Selective inhibition of interleukin 6 receptor decreased inflammatory cytokines and increased proteases in an experimental model of critical calvarial defect

• Published in: Brazilian journal of medical and biological research Vol. 57; p. e13913
• Main Authors: Melo, R C O, Martins, A A, Vieira, G H A, Andrade, R V S, Silva, D N A, Chalmers, J, Silveira, T M, Pirih, F Q, Araújo, V S, Silva, J S P, Lopes, M L D S, Leitão, R F C, Araújo Júnior, R F, Silva, I L G, Silva, L J T, Barbosa, E G, Araújo, A A
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01.08.2024; Associação Brasileira de Divulgação Científica
• Subjects: Analysis; Animals; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; BIOLOGY; Bone; Bone diseases; Care and treatment; Collagen; Critical defect; Cytokines; Cytokines - metabolism; Disease Models, Animal; Gene expression; Health aspects; Immunohistochemistry; Inflammation; Interleukin-6; Interleukins; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Peptide Hydrolases - metabolism; Physiological aspects; Proteases; Random Allocation; Rats; Rats, Wistar; Receptors, Interleukin-6 - antagonists & inhibitors; Skull - drug effects; Tocilizumab; X-Ray Microtomography; Brazil; Inflammation; Bone; Critical defect; Cytokines; Tocilizumab
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X2024e13913

Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.