Targeting interleukin-6 in immune-mediated inflammatory diseases: Current strategies and emerging technologies

Abstract

Immune-mediated inflammatory diseases (IMIDs) refer to a heterogeneous group of conditions driven by dysregulated immune responses that affect multiple organs and systems, leading to substantial morbidity and premature mortality. Accumulating evidence indicates that excessive interleukin-6 (IL-6) production and aberrant activation of downstream signaling pathways play central roles in sustaining chronic inflammation and acute hyperinflammatory states. This review aims to summarize the current understanding of IL-6 biology and signaling modes, and critically evaluate therapeutic strategies targeting IL-6 across multiple IMIDs. We discuss the clinical efficacy and limitations of approved IL-6 signaling inhibitors in chronic immune-mediated disorders and acute systemic inflammation, as well as emerging evidence supporting pathway-selective interventions such as IL-6 trans-signaling blockade. In addition, recent advances in therapeutic innovation, including proteolysis-targeting chimeras, clustered regularly interspaced short palindromic repeats (CRISPR)-based genome engineering, RNA interference, and nanotechnology-enabled drug delivery platforms, are highlighted for their potential to improve specificity, tissue targeting, and durability of IL-6 modulation. In summary, these developments reflect a shift from uniform cytokine inhibition toward more selective and physiologically informed approaches, which may ultimately refine IL-6 targeted therapies and improve outcomes across diverse IMIDs.