IL-6

IL-6 is a pleiotropic cytokine that regulates immune response, acute inflammation, tissue regeneration, metabolism, and stromal activation[1][2]. Mechanistically, IL-6 binds IL-6Rα and recruits gp130, activating JAK/STAT3 signaling and downstream transcriptional programs[1][3]. Disease relevance depends strongly on receptor context: membrane IL-6Rα supports classic signaling, whereas soluble IL-6Rα enables trans-signaling in gp130-expressing cells and drives pro-inflammatory activity[1][4]. Compared with these receptor forms, gp130 is broadly expressed, while IL-6R expression is restricted to selected cells such as hepatocytes and leukocytes, explaining cell-type-selective responsiveness[1]. In vascular endothelial cells, IL-6 trans-signaling induces MCP-1 through coordinated JAK/STAT3 and PI3K/AKT activation[5]. In proliferative vitreoretinopathy models, IL-6 promotes retinal pigment epithelial proliferation and epithelial-mesenchymal transition through JAK1/STAT3 signaling[6]. For experimental intervention, tocilizumab, a humanized anti-IL-6R antibody, blocks IL-6 signaling and improves rheumatoid arthritis outcomes in controlled clinical studies[7][8].
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