Cytokines of the interleukin-6 family as emerging targets in inflammatory bowel disease

ABSTRACT

Introduction

Inflammatory bowel disease (IBD) is an umbrella term that includes different chronic inflammatory diseases of the gastrointestinal tract, most commonly Crohn’s disease and ulcerative colitis. IBD affects more than 6 million people worldwide and constitutes not only a debilitating disease for the patients, but also a significant factor for society due to costs for health care and reduced working capacity. Despite the introduction of biologicals for the treatment of IBD, the identification of novel targets that could lead to novel therapeutics is still needed.

Areas covered

In this review, we summarize current knowledge about the interleukin-6 family of cytokines as potential therapeutic targets for improving the therapy of patients with IBD. We discuss cytokines like IL-6 itself for which therapeutics such as inhibitory monoclonal antibodies have already entered the clinics, but also focus on other family members whose therapeutic potential has not been explored yet.

Expert opinion

The different cytokines of the IL-6 family offer multiple therapeutic targets that can potentially be used to treat patients with inflammatory bowel disease, but unwanted side effects like inhibition of epithelial regeneration have to be considered.

KEYWORDS:

• Classic signaling
• gp130
• interleukin-6
• interleukin-11
• STAT3
• trans-signaling

Article highlights

• IL-6 family cytokines are important soluble proteins with crucial roles in inflammatory diseases.

• Therapeutics targeting IL-6 are already in clinical studies for IBD.

• Differentiation between classic and trans-signaling of IL-6 is important for the safety of therapeutic intervention.

• IL-11 and OSM are novel therapeutic targets whose potential should be explored.

• First results suggest that also targeting of LIF and CT-1 could bear therapeutic potential.

Disclosure of interest

C Garbers has received a research grant from Corvidia Therapeutics (Waltham, MA, U.S.A.) and has acted as a consultant/speaker for AbbVie and NovoNordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Astrid Schneider for excellent assistance.

Additional information

Funding

This paper was not funded.