Interleukin-6 (IL6) is a 26-kD secreted protein belonging to the pro-inflammatory cytokine family. It has pleiotropic functions, stimulating B cells to produce antibodies, inducing acute-phase proteins for inflammation, and playing a role in cell proliferation and differentiation [1,2]. IL6 signaling occurs through a complex of IL6, the transmembrane IL6-receptor (mIL6R) or soluble IL6-receptor (sIL6R), and the signal-transducing subunit gp130, with three modes: classic, trans-signaling, and trans-presentation [2]. It is involved in the regulation of the immune system, nervous system, liver regeneration, and metabolic control of the body [4].

In a murine multiple trauma model, modulation of IL6 signaling (both classic and trans-signaling) via application of an IL6-R antibody reduced IL6 and sIL6-R serum levels, neutrophil infiltration, and end-organ damage, suggesting a regulatory role of IL6 signaling pathways in polytrauma with hemorrhagic shock as a major trigger of the inflammatory response [3]. In colon carcinoma, although knocking out IL6 in colon tumor cells did not significantly alter tumor growth in wild-type (WT) mice, overexpression of IL6 in colon tumor cells increased tumor growth in vivo, indicating that a high tumor local IL6 threshold is essential for IL6 function in colon tumor promotion [5]. In amyotrophic lateral sclerosis patients, serum IL6 levels negatively correlated with functional status and respiratory function, but only in patients carrying the IL6R358Ala variant that mediates pro-inflammatory trans-signaling, suggesting targeted therapeutic approaches may be more advantageous for this group [6].

In conclusion, IL6 is a key cytokine with diverse functions in multiple biological processes. Model-based research, such as the use of KO/CKO mouse models, has revealed its significance in trauma-related immune responses, cancer growth, and neurodegenerative disease progression. These findings contribute to our understanding of the underlying mechanisms of related diseases and may guide the development of targeted therapies.