As a main pro-inflammatory factor, the up-regulation of TNF-α in RA patients plays a pivotal role in RA pathogenesis. The process of TNF production starts with the binding of a ligand( which is commonly a microbial p...As a main pro-inflammatory factor, the up-regulation of TNF-α in RA patients plays a pivotal role in RA pathogenesis. The process of TNF production starts with the binding of a ligand( which is commonly a microbial product) to a cell surface Toll receptor, which stimulates a signal transduction pathway that activates NF - κB transcription factors. Activated NF - κB enters nuclei and induces the transcription of genes associated with inflammation, including those coding for TNF. The production of TNF and other inflammatory cytokines serves to recruit other inflammatory cells, which in turn release cytokines and subsequently amplify the immune response. TNF exerts its effect via binding of TNFRland TNFR2 receptors. Many experimental and clinical study have proved the effectiveness of TNF - αa ctivity blockade. Recent therapeutic interventions, including TNF - α and IL - 1 inhibitors, strongly support the importance of cytokines in RA. The mechanism of anti - TNF - α action in vivo is complex and probably includes suppression of other pro - inflammatory cytokines, decreased synovial cellular infiltration, interference with osteoclast activation, and decreased angiogenisis. Studies using anti -TNF agents clearly show that they can slow or prevent the progression of bone and cartilage damage in RA. This activity probably involves suppression of osteoclasts in joint lesions. Etanereept, Infliximab and adalimumab are the three main biologic agents that were fo-cused on clinically at present.展开更多
文摘As a main pro-inflammatory factor, the up-regulation of TNF-α in RA patients plays a pivotal role in RA pathogenesis. The process of TNF production starts with the binding of a ligand( which is commonly a microbial product) to a cell surface Toll receptor, which stimulates a signal transduction pathway that activates NF - κB transcription factors. Activated NF - κB enters nuclei and induces the transcription of genes associated with inflammation, including those coding for TNF. The production of TNF and other inflammatory cytokines serves to recruit other inflammatory cells, which in turn release cytokines and subsequently amplify the immune response. TNF exerts its effect via binding of TNFRland TNFR2 receptors. Many experimental and clinical study have proved the effectiveness of TNF - αa ctivity blockade. Recent therapeutic interventions, including TNF - α and IL - 1 inhibitors, strongly support the importance of cytokines in RA. The mechanism of anti - TNF - α action in vivo is complex and probably includes suppression of other pro - inflammatory cytokines, decreased synovial cellular infiltration, interference with osteoclast activation, and decreased angiogenisis. Studies using anti -TNF agents clearly show that they can slow or prevent the progression of bone and cartilage damage in RA. This activity probably involves suppression of osteoclasts in joint lesions. Etanereept, Infliximab and adalimumab are the three main biologic agents that were fo-cused on clinically at present.
