文献类型：期刊文献

英文题名：Molecular mechanisms of biologic and targeted synthetic antirheumatic drugs in rheumatoid arthritis

作者：Li, Longcan[1];Chen, Xin[2];Wang, Shengpeng[1];Li, Zhengle[1];Xie, Xingwen[3]

第一作者：Li, Longcan

通信作者：Xie, XW[1]

机构：[1]Gansu Univ Chinese Med, Coll Clin Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Affiliated Hosp, Dept Geriatr Orthoped, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Prov Hosp TCM, Lanzhou 730050, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp TCM, Lanzhou 730050, Gansu, Peoples R China.

年份：2026

卷号：91

起止页码：125

外文期刊名：CYTOKINE & GROWTH FACTOR REVIEWS

收录：;Scopus(收录号：2-s2.0-105047878701);WOS:【SCI-EXPANDED(收录号:WOS:001854387600001)】；

基金：This work was supported by the National Natural Science Foundation of China [grant number 82374491]; the Gansu Provincial Traditional Chinese Medicine Research Project [grant number GZKZ - 2024-9] ; and the Gansu Famous Traditional Chinese Medicine Legacy Studio Construction Project [grant number 2023-168] .

语种：英文

外文关键词：Rheumatoid arthritis; Cytokine signaling; TNF; Interleukin-6; JAK-STAT; Synovial fibroblasts; RANKL; Synovial pathotypes

摘要：Rheumatoid arthritis is sustained by a synovial cytokine network that acquires the capacity to maintain inflammation independently of its initiating stimulus. The biologic and targeted synthetic antirheumatic drugs developed over the past two decades each interrupt this network at a defined molecular node, and their differential effects in patients therefore reveal how the network is organized. This review is structured around that principle, treating each agent as a probe of the axis it targets rather than as a therapeutic option. Following an account of the synovial signaling nodes on which diverse cytokines converge, four axes are examined: TNF-NF kappa B, where receptor-level bifurcation between inflammatory and regulatory signaling defines the class; IL-6 and JAK-STAT, where classic and trans-signaling separate pathogenic from homeostatic function; costimulatory and lymphocyte-directed signaling, targeted by CTLA4-Ig and B-cell depletion; and the effector axes of tissue destruction driven by RANKL and GM-CSF. A recurring theme is that persistent synovitis reflects failure of the circuits that normally terminate cytokine signaling, and that fibroblast programs, once epigenetically imprinted, become progressively independent of the cytokines that established them. Synovial pathotypes correspond to differences in which axis is transcriptionally dominant, providing a biological rationale for stratified therapy; the same framework identifies a fibroblast-dominant state refractory to every current agent. Whether axis dominance is fixed or shifts under treatment remains the central unresolved question determining whether mechanismguided therapy is clinically achievable.