Журнал клинической патологии и лабораторной медицины


The role of IL-6 in cancer, autoimmune disease, and inflammation

Michael Panwar

Immune responses, inflammation, haematopoiesis, bone metabolism, and embryonic development are all impacted by IL-6. IL-6 contributes to chronic inflammation and even the corona virus disease cytokine storm in 2019. Chronic inflammation and the cytokine storm are uncontrolled inflammatory reactions, whereas acute inflammation during the immune response and wound healing is a well-controlled response. Inflammation is mostly regulated by immune and non-immune cells, cytokines including IL-1, IL-6, and tumour necrosis factor alpha, as well as transcription factors like nuclear factor-kappa B (NF-B) and signal transducer and activator of transcription. Synergistic interactions between NF-B and STAT3 cause NF-B to become overactive, which in turn triggers the production of a number of inflammatory cytokines. The simultaneous activation of NF-B and STAT3 in non-immune cells causes a positive feedback loop of NF-B activation by the IL-6-STAT3 axis because IL-6 is an NF-B target. The local initiation model postulates that local initiators, such as senescence, obesity, stressors, infections, injuries, and smoking, trigger diseases by promoting interactions between non-immune cells and immune cells. This positive feedback loop is known as the IL-6 amplifier and is a key player in the model. This approach challenges the assumption that tissue-specific immune tolerance breakdown and oncogenesis are caused by, respectively, oncogenic mutations and autoimmunity. It is clear that the IL-6-STAT3 axis is an important target for treating illnesses since it is triggered by a number of local initiators.