Could IL-6 inhibitors be the future of DVT therapy? A new era in therapeutic strategies

Objective This mini review aims to synthesize current evidence on signaling mechanisms particularly classical and trans-signaling pathways, and also to evaluate the therapeutic potential of targeting IL-6 in thrombotic disorders.Methods The research design is to provide a focused and systematic literature survey of peer-reviewed studies focusing on the role of IL-6 signaling in DVT. Databases including PubMed, Scopus, and Web of Science were utilized using relevant keywords like “interleukin-6”, “gp-130̎”, “endothelial dysfunction”, “IL-6 inhibitors”, “deep vein thrombosis”, and “IL-6 trans-signaling”. The shortlisted articles were critically evaluated to integrate current knowledge on IL-6-mediated thrombo-inflammation, especially focusing on emerging therapeutic strategies such as monoclonal IL-6 receptor inhibitors and selective blockade of IL-6 trans signaling using sgp130Fc.Results Evidences demonstrated that sustained IL-6 trans-signaling contributes to endothelial dysfunction, hypercoagulability and thrombus formation. Pre-clinical and clinical studies indicate that IL-6 pathway inhibition can reduce thrombus burden, improve endothelial function and attenuate inflammatory and pro-coagulant states. Selective inhibition of IL-6 trans-signaling via sgp130Fc appears particularly promising, as it suppresses pathological inflammation while preserving the protective effects of classical IL-6 signaling.Conclusions Although IL-6 inhibitors are not currently approved for clinical management of DVT, growing evidence supports IL-6 as a key therapeutic target in thrombo-inflammatory disorders. Balancing the pleiotropic effects of IL-6 remains a challenge, however, selective modulation of IL-6 signaling, and synergy with anticoagulants, represent a promising strategy for improving DVT treatment outcomes. Further translation and clinical studies are required to optimize therapeutic approaches and patient selection.