Targeting Interleukin-6 Pathway in the Treatment of Immune-mediated Inflammatory Diseases： from Bench to Clinic
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0501
- VernacularTitle:靶向IL-6通路治疗免疫介导的炎症性疾病：从机制到临床
- Author:
Tao WU
1
;
Lie DAI
1
Author Information
1. Department of Rheumatology and Immunology， Sun Yat-sen Memorial Hospital， Sun Yat-sen University， Guangzhou 510120， China
- Publication Type:Review
- Keywords:
interleukin-6;
immune-mediated inflammatory diseases;
cytokines;
targeted therapy;
medication management
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(5):721-729
- CountryChina
- Language:Chinese
-
Abstract:
Immune-mediated inflammatory diseases （IMIDs） are a broad category of chronic inflammatory disorders caused by abnormal activation of immune system， characterized by an imbalance between excessive release of proinflammatory cytokines and insufficient anti-inflammatory regulatory signals. Interleukin-6 （IL-6）， a pleiotropic cytokine， serves as a "molecular bridge" connecting innate immunity and adaptive immunity due to its unique "trinity" signaling mechanism （classical signaling， trans-signaling， and trans-presenting pathway）. The IL-6 signaling pathway drives acute-phase inflammatory responses and participates in the activation of innate immunity and the regulation of adaptive immunity through multiple mechanisms， which is the key pathway that leads to the inflammatory responses and multi-organ damage of IMIDs.Therapeutic agents targeting the IL-6 pathway， which inhibit aberrant signaling by blocking IL-6/IL-6 receptor/gp130 signaling axis， have been widely used in the clinical practice for treating various IMIDs such as rheumatoid arthritis， juvenile idiopathic arthritis/ adult-onset Still's disease， giant cell arteritis， Takayasu’s arteritis and Castleman's disease. Currently approved medications in this class include tocilizumab， satralizumab， sarilumab， and siltuximab. However， IL-6 inhibitors also encounter various safety challenges in clinical applications， including increased infection risk， metabolic abnormalities and cardiovascular risks， hypofibrinogenemia， and DRESS syndrome. This review systematically elaborates on the molecular mechanism of the IL-6 signaling pathway and its pathogenic role in IMIDs， the progress in the development of targeted drugs， and the safety issues in clinical applications， aiming to promote the transformation of IL-6 targeted therapy from bench to clinic， provide a "mechanism-guided individualized" framework for optimizing treatment decisions， and point out the direction for the establishment of a long-term safety management system.
