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.

2020-06-01·Current Opinion in Pharmacology2区 · 医学

Recent advances in the role of interleukin-6 in health and disease

2区 · 医学

Review

作者: Townsend, Logan K ; Peppler, Willem T ; Wright, David C

Interleukin-6 (IL-6) is a pleotropic cytokine, and in this review, we highlight recent studies focusing on the role of IL-6 in health and disease. IL-6 is known as an exercise-inducible myokine, and in rodents it was identified that a lactate-dependent increase in protease activity mediates IL-6 release from skeletal muscle, which acts in both an autocrine and paracrine roles. In humans, a series of publications observed that blocking IL-6 during exercise training prevented beneficial adaptations, such as reductions in visceral and epicardial fat mass. Independent of exercise, IL-6 impacts postprandial physiology, as demonstrated by a slowing of gastric emptying rate and improving glucose homeostasis. Finally, an engineered cytokine harnessing the biology of IL-6, termed IC7Fc, was found to have beneficial impacts on numerous health outcomes. Together, these recent advances indicate that IL-6 has a multifaceted, and perhaps beneficial, role in health and disease.

2019-10-03·Nature1区 · 综合性期刊

Treatment of type 2 diabetes with the designer cytokine IC7Fc

1区 · 综合性期刊

Article

作者: Allen, Tamara L ; Cowley, Michael A ; Drucker, Daniel J ; Kammoun, Helene ; Thai, Le May ; Bruce, Clinton R ; Mellet, Natalie A ; Keating, Damien J ; Sun, Emily ; Estevez, Emma ; Lee, Robert S ; Krippner, Guy ; Egan, Casey ; Yang, Christine ; Cooney, Gregory J ; O'Reilly, Liam ; Findeisen, Maria ; Pal, Martin ; Brandon, Amanda E ; Kraakman, Michael J ; Rose-John, Stefan ; Grötzinger, Joachim ; Kowalski, Greg M ; Febbraio, Mark A ; Kimber, Erica T ; Garbers, Christoph ; Sligar, James ; Watt, Kevin I ; Risis, Steve ; Baldock, Paul A ; Adams, Timothy E ; Young, Richard L ; Baggio, Laurie L ; Henstridge, Darren C ; Cron, Lena ; Gregorevic, Paul ; Biden, Trevor J ; Meikle, Peter J

The gp130 receptor cytokines IL-6 and CNTF improve metabolic homeostasis but have limited therapeutic use for the treatment of type 2 diabetes. Accordingly, we engineered the gp130 ligand IC7Fc, in which one gp130-binding site is removed from IL-6 and replaced with the LIF-receptor-binding site from CNTF, fused with the Fc domain of immunoglobulin G, creating a cytokine with CNTF-like, but IL-6-receptor-dependent, signalling. Here we show that IC7Fc improves glucose tolerance and hyperglycaemia and prevents weight gain and liver steatosis in mice. In addition, IC7Fc either increases, or prevents the loss of, skeletal muscle mass by activation of the transcriptional regulator YAP1. In human-cell-based assays, and in non-human primates, IC7Fc treatment results in no signs of inflammation or immunogenicity. Thus, IC7Fc is a realistic next-generation biological agent for the treatment of type 2 diabetes and muscle atrophy, disorders that are currently pandemic.

100 项与 IC-7Fc (University of Kiel) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
2型糖尿病	临床前	澳大利亚	Monash University	-
2型糖尿病	临床前	德国	University of Kiel	-
肌肉萎缩	临床前	德国	University of Kiel	-
肌肉萎缩	临床前	澳大利亚	Monash University	-