Interleukin-6 (IL6) is a 26-kD secreted protein and a member of the pro-inflammatory cytokine family. It stimulates B cells to produce antibodies, induces acute-phase proteins responsible for acute inflammation, and plays a crucial role in cell proliferation and differentiation. IL6 signaling occurs through three modes: classic (binding to transmembrane IL-6 receptor, mIL-6R), trans-signaling (binding to soluble IL-6 receptor, sIL-6R), and trans-presentation. It activates multiple pathways like JAK/STAT, and its dysregulation is linked to inflammatory, autoimmune disorders, and cancer [1,2].

In a murine multiple trauma model, modulation of IL6 signaling (both classic and trans-signaling) was attempted. Blocking IL6 signaling via IL6-R antibody application significantly reduced IL6 and sIL6-R serum levels, neutrophil infiltration in shock organs, and end-organ damage. This shows the regulatory role of IL6 signaling pathways in polytrauma, with hemorrhagic shock being a major trigger of the inflammatory response [3]. In colon carcinoma, although tumor cells, T cells, and myeloid cells express IL6, polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are the primary IL6-expressing cell type. IL6 activates STAT3 to up-regulate DNMT1 and DNMT3b expression in colon tumor cells. Knocking out IL6 in colon tumor cells did not significantly alter tumor growth in wild-type mice, but overexpression of IL6 in colon tumor cells increased tumor growth in vivo, indicating a high local IL6 threshold is essential for its tumor-promoting function [4].

In conclusion, IL6 is a pleiotropic cytokine with diverse functions in immune and non-immune cells. Its dysregulation is associated with multiple diseases. Mouse models, such as the trauma model and the colon carcinoma model, have revealed its role in inflammation and tumor growth, providing insights into potential therapeutic strategies for related diseases.