Interleukin-6 (IL-6) Receptor Antagonist Protects Against Rheumatoid Arthritis

Abstract

BackgroundThe aim of this study was to investigate the protective effect of interleukin-6 (IL-6) receptor antagonist tocilizumab (TCZ) on rheumatoid arthritis (RA) and its related mechanism.Material/MethodsThirty RA patients receiving long-term methotrexate therapy at moderate and severe active stages were selected and treated with TCZ 8 mg/kg/time iv gtt intravenously guttae every 4 weeks. Peripheral blood was extracted before and 24 weeks after TCZ treatment. Peripheral blood mononuclear cells (PBMC) were collected by density gradient centrifugation. Flow cytometry was used to detect the ratio of CD4 naïve T cells and CD4 memory T cells, Th17 cells, and Treg cells in PBMC. DAS28 score, CRP, RF, and CCP levels in patients were evaluated.ResultsCompared with before treatment, IL-6 receptor antagonist TCZ significantly improved patients’ condition, including DAS28 score, CRP, RF, and CCP levels (P<0.01). Furthermore, TCZ obviously upregulated CD4 naïve T cells proportion and decreased CD4 memory T cells ratio (P<0.01). TCZ also markedly reduced the proportion of Th17 cells and increased the proportion of Treg cells (P<0.01).ConclusionsTCZ can treat RA patients through regulating the ratio of CD4 naïve T cells, CD4 memory T cells, Th17 cells, and Treg cells in PBMC.

Anti-Inflammatory Effects of HDL in Mice With Rheumatoid Arthritis Induced by Collagen

“…Additionally, HDL treatment inhibited the expression of TNF-α in CIA mice, which is in accordance with our previous study (16). We also investigated the expression level of IL-6, which also plays a crucial role in the development and treatment of RA (17, 18). Increased level of IL-6 in CIA mice was also downregulated by HDL.…”

Leptin‐induced migration and angiogenesis in rheumatoid arthritis is mediated by reactive oxygen species

“…Inflammatory cytokines such as TNF‐α, IL‐6 and IL‐1 are important mediators in driving inflammation and joint destruction in RA. TNF and IL‐1 stimulate synoviocytes and chondrocytes to release matrix metalloproteinases and other proteinases, and up‐regulate the expression of proinflammatory genes, resulting in elevated production of various proinflammatory mediators . IL‐6 promotes survival of B cells and their differentiation into autoantibody‐secreting long‐lived plasma cells leading to RA joint destruction .…”

The Balance of Th17 versus Treg Cells in Autoimmunity

“…Therapeutic approaches aimed at neutralizing Th17-related cytokines (including IL-6, TNF-α, IL-17, and IL-23) using monoclonal antibodies have been quite successful [ 118 , 119 ]. Monoclonal antibodies against the human IL-6R, tocilizumab and sarilumab, affect the ratio of Th17/Treg cells by reducing Th17 but increasing Treg cell levels in RA patients [ 120 , 121 , 122 ]. In addition, therapies designed to target RORγt, STAT3, Foxp3, and Foxo1 using small molecules are being developed [ 118 , 119 ].…”