Blocking IL-17: A Promising Strategy in the Treatment of Systemic Rheumatic Diseases

Abstract

Systemic rheumatic diseases are a heterogeneous group of autoimmune disorders that affect the connective tissue, characterized by the involvement of multiple organs, leading to disability, organ failure and premature mortality. Despite the advances in recent years, the therapeutic options for these diseases are still limited and some patients do not respond to the current treatments. Interleukin-17 (IL-17) is a cytokine essential in the defense against extracellular bacteria and fungi. Disruption of IL-17 homeostasis has been associated with the development and progression of rheumatic diseases, and the approval of different biological therapies targeting IL-17 for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) has highlighted the key role of this cytokine. IL-17 has been also implicated in the pathogenesis of systemic rheumatic diseases, including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS) and systemic sclerosis (SSc). The aim of this review is to summarize and discuss the most recent findings about the pathogenic role of IL-17 in systemic rheumatic and its potential use as a therapeutic option.

IL‐17 drives salivary gland dysfunction via inhibiting TRPC1‐mediated calcium movement in Sjögren’s syndrome

“…The blockade of IL-17 has been shown to be effective in the treatment of various autoimmune diseases. 39 Here, our findings that local salivary cannulation of IL-17 neutralising antibodies significantly improves salivary secretion during ESS development further indicate local IL-17 in SG as a promising therapeutic target for treating xerostomia in pSS patients.…”

Vaccination by Two DerG LEAPS Conjugates Incorporating Distinct Proteoglycan (PG, Aggrecan) Epitopes Provides Therapy by Different Immune Mechanisms in a Mouse Model of Rheumatoid Arthritis

“…Rosenthal et al [ 3 ] reviewed and discussed other therapies for RA in relation to LEAPS conjugates and the differences in mechanism of action and targets. A sampling of more recent papers within the last few years of research and reviews of proposed or experimental modern therapies using cytokines targeted via soluble receptors or monoclonal antibodies for IL-6, IL-17 and Janus kinase inhibitors show promises but still limitations of unidirectional and all downward [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. We have developed a peptide vaccine technology that can be protective or therapeutic, which we refer to as Ligand Epitope Antigen Presentation System (LEAPS).…”

Amino terminal recognition by a CCR6 chemokine receptor antibody blocks CCL20 signaling and IL-17 expression via β-arrestin

“…While antibody 1C6 inhibits arrestin pathway, antibody KM4703 inhibits G protein dependent pathway and it could be indicating that inhibition of arrestin pathway produces a greater response that inhibition of G protein dependent pathways. IL-17 inhibitors are a new and promising therapeutic option for treatment of inflammatory diseases and three anti-IL17 monoclonal antibodies, secukinumab, brodalumab and ixekizumab, are approved for psoriasis treatment [ 42 ]. Based on the results obtained, 1C6 antibody it could be an alternative to treatments with anti-IL-17.…”