New insights into IL-6 family cytokines in metabolism, hepatology and gastroenterology

In this Review, the authors describe the biology of IL-6 family cytokines relevant to metabolism, liver disease and gastrointestinal disease, and discuss the potential of IL-6 family members as therapeutic agents in these areas. IL-6 family cytokines are defined by the common use of the signal-transducing receptor chain glycoprotein 130 (gp130). Increasing evidence indicates that these cytokines are essential in the regulation of metabolic homeostasis as well as in the pathophysiology of multiple gastrointestinal and liver disorders, thus making them attractive therapeutic targets. Over the past few years, therapies modulating gp130 signalling have grown exponentially in several clinical settings including obesity, cancer and inflammatory bowel disease. A newly engineered gp130 cytokine, IC7Fc, has shown promising preclinical results for the treatment of type 2 diabetes, obesity and liver steatosis. Moreover, drugs that modulate gp130 signalling have shown promise in refractory inflammatory bowel disease in clinical trials. A deeper understanding of the main roles of the IL-6 family of cytokines during homeostatic and pathological conditions, their signalling pathways, sources of production and target cells will be crucial to the development of improved treatments. Here, we review the current state of the role of these cytokines in hepatology and gastroenterology and discuss the progress achieved in translating therapeutics targeting gp130 signalling into clinical practice.

Automated summary

IL-6 family cytokines play crucial roles in metabolism, liver disease, and gastrointestinal disease, with potential as therapeutic targets. Therapies modulating gp130 signaling have shown promise in various clinical settings, including obesity, cancer, and inflammatory bowel disease.