Comparative study of anti-VEGF Ranibizumab and Interleukin-6 receptor antagonist Tocilizumab in Adjuvant-induced Arthritis


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Abstract

Although the precise etiology of Rheumatoid arthritis (RA) remains obscure, heightened immune response is thought to play a vital role in provoking joint inflammation and bone erosion. This study aims at comparatively evaluating the effects of two monoclonal antibodies Ranibizumab (RANI) as anti-VEGF antibody and Tocilizumab (TCZ) as interleukin-6 receptor (IL-6R) antagonist, against adjuvant induced arthritis in rats. CFA-induced arthritic rats were treated for three consecutive weeks with Methotrexate (MTX), TCZ and RANI monotherapy. Clinical assessment of RA, bone erosion, inflammatory, angiogenic and apoptotic markers were determined to assess the anti-arthritic effect. Liver enzymes and histopathological examination of liver and spleen were assessed to evaluate the toxicity profile of the tested therapeutic agents. MTX, TCZ and RANI monotherapy significantly enhanced the anti-arthritic parameters in comparison with the Complete Freund's Adjuvant (CFA)-induced arthritic rats through significant reduction of ankle and paw swelling. Also, they significantly reduced inflammatory, angiogenic and apoptotic markers. Importantly, Ranibizumab showed better effect than the standard anti-rheumatic drugs Methotrexate (MTX) or Tocilizumab (TCZ) in bone protection and cartilage health; hence proves to be a promising new therapeutic agent for RA.Graphical abstractRA development starts with triggering immune cells such as Macrophages and Neutrophils. These cells produced different types of cytokines such as IL-6 and TNF-α. IL-6 with TNF-α participate in T-cells differentiation into Th-17 that produce IL-17. IL-17 plays a synergistic role with other cytokines in immune cells differentiation. Il-6 is also involved in differentiation of B-cells into plasma cells. Furthermore, IL-6 and IL-1b enhance synovocytes proliferation that lead to angiogenesis, apoptosis and cartilage destruction and bone erosion through production of different cytokines, markers and enzymes such as VEGF, TGFβ, COX-II, RANKL and MMPs.HighlightsRANI significantly reduced ankle and paw swelling in CFA-induced arthritic rats.Anti-inflammatory of RANI was confirmed beside its anti-angiogenic effect.RANI also produced anti-apoptotic and bone protective effects.RANI modulated the interplay between different arthritic machineries.RANI showed better bone protective effect than MTX or TCZ monotherapy.

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