Targeting IL-6 trans-signalling: past, present and future prospects

Area of Science:

• Immunology
• Molecular Biology
• Pharmacology

Background:

• Interleukin-6 (IL-6) is a cytokine crucial in immune responses and disease.
• IL-6 exerts its effects through classical signalling, IL-6 trans-signalling, and cluster signalling.
• IL-6 trans-signalling is increasingly recognized as a major driver of disease pathogenesis.

Purpose of the Study:

• To review the biological outcomes of IL-6-mediated signalling.
• To explore the therapeutic potential of targeting IL-6 trans-signalling.
• To discuss advancements in developing selective IL-6 trans-signalling inhibitors.

Main Methods:

• Review of existing literature on IL-6 signalling pathways.
• Analysis of preclinical and clinical data for IL-6 trans-signalling inhibitors.
• Discussion of technological developments in inhibitor design.

Main Results:

• IL-6 trans-signalling is a predominant mechanism in disease.
• Selective inhibitors like sgp130 have shown efficacy in preclinical models.
• Olamkicept (sgp130Fc variant) demonstrated promising results in inflammatory bowel disease clinical trials.

Conclusions:

• Targeting IL-6 trans-signalling offers a promising therapeutic strategy for various diseases.
• Next-generation inhibitors with enhanced affinity and selectivity are under development.
• Further research into IL-6 signalling blockade holds significant clinical potential.