Effects of Tocilizumab on Intervertebral Disc Degeneration, Cell Senescence and Inflammation via BMP-2, Hif-1, IL-1 and SOX9

Background and Objective: Immunosuppressive tocilizumab (TCZ), which is frequently used in the treatment of rheumatoid arthritis, can have many side effects as well as an uncontrolled inflammatory response. This study aimed to evaluate the effect of tocilizumab (TCZ) administered to intervertebral disc (IVD) tissues in vitro on the proinflammatory cytokines and proteins of degeneration, senescence and inflammation-related signaling pathways at the pharmaco-molecular level. Materials and Methods: Primary cell cultures were prepared using human IVD tissues obtained during lumbar microdiscectomy. Untreated groups served as the control and TCZ-treated groups as the study sample. Analyses were performed using a commercial kit, supravital and fluorescent dyes. Changes in bone morphogenetic protein (BMP)-2, hypoxia-inducible factor (Hif)1-alpha (Hif1-alpha), interleukin (IL)-1 beta (IL-1 beta) and sex-determining region Y (SRY)-box 9 (SOX9) protein expressions were evaluated using western blotting. An alpha value of less than 0.05 was considered significant. Results: Proliferation decreased in the samples treated with TCZ (10 mu g mLG1 ) on day 15 (p<0.05). Protein expressions of BMP-2, Hif-1 alpha, IL-1 beta and SOX9, which play a vital role in anabolic and catabolic pathways, changed in samples treated with TCZ (10 mu g mLG1 ). Conclusion: This change was statistically significant (p<0.05). Therefore, results concluded that the inflammation, extracellular matrix degradation and nucleus pulposus degeneration after disc herniation are controlled by BMP-2, Hif-1 alpha, IL-1 beta and SOX9.