IL-6 in inflammation, autoimmunity and cancer #MMPMID33337480
Hirano T
Int Immunol 2021[Mar]; 33 (3): 127-148 PMID33337480show ga
IL-6 is involved both in immune responses and in inflammation, hematopoiesis, bone metabolism and embryonic development. IL-6 plays roles in chronic inflammation (closely related to chronic inflammatory diseases, autoimmune diseases and cancer) and even in the cytokine storm of corona virus disease 2019 (COVID-19). Acute inflammation during the immune response and wound healing is a well-controlled response, whereas chronic inflammation and the cytokine storm are uncontrolled inflammatory responses. Non-immune and immune cells, cytokines such as IL-1beta, IL-6 and tumor necrosis factor alpha (TNFalpha) and transcription factors nuclear factor-kappa B (NF-kappaB) and signal transducer and activator of transcription 3 (STAT3) play central roles in inflammation. Synergistic interactions between NF-kappaB and STAT3 induce the hyper-activation of NF-kappaB followed by the production of various inflammatory cytokines. Because IL-6 is an NF-kappaB target, simultaneous activation of NF-kappaB and STAT3 in non-immune cells triggers a positive feedback loop of NF-kappaB activation by the IL-6-STAT3 axis. This positive feedback loop is called the IL-6 amplifier (IL-6 Amp) and is a key player in the local initiation model, which states that local initiators, such as senescence, obesity, stressors, infection, injury and smoking, trigger diseases by promoting interactions between non-immune cells and immune cells. This model counters dogma that holds that autoimmunity and oncogenesis are triggered by the breakdown of tissue-specific immune tolerance and oncogenic mutations, respectively. The IL-6 Amp is activated by a variety of local initiators, demonstrating that the IL-6-STAT3 axis is a critical target for treating diseases.
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Int+Immunol 2021 ; 33 (3): 127-148
