The Interleukine-17 Cytokine Family: Role in Development and Progression of Spondyloarthritis, Current and Potential Therapeutic Inhibitors

Abstract

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory rheumatic diseases with a predilection for the spinal and sacroiliac joints, which include axial spondyloarthritis, psoriatic arthritis, reactive arthritis, arthritis associated with chronic inflammatory bowel disease, and undifferentiated spondyloarthritis. The prevalence of SpA in the population varies from 0.5 to 2%, most commonly affecting young people. Spondyloarthritis pathogenesis is related to the hyperproduction of proinflammatory cytokines (TNFα, IL-17А, IL-23, etc.). IL-17A plays a key role in the pathogenesis of spondyloarthritis (inflammation maintenance, syndesmophites formation and radiographic progression, enthesites and anterior uveitis development, etc.). Targeted anti-IL17 therapies have established themselves as the most efficient therapies in SpA treatment. The present review summarizes literature data on the role of the IL-17 family in the pathogenesis of SpA and analyzes existing therapeutic strategies for IL-17 suppression with monoclonal antibodies and Janus kinase inhibitors. We also consider alternative targeted strategies, such as the use of other small-molecule inhibitors, therapeutic nucleic acids, or affibodies. We discuss advantages and pitfalls of these approaches and the future prospects of each method.

Characteristics of mucin hypersecretion in different inflammatory patterns based on endotypes of chronic rhinosinusitis

“…Chen et al 111 reported that IL-17 directly regulates MUC5B gene expression at the promoter level via the ERK1/2 signaling pathway or via IL-6 paracrine or autocrine loops in primary human tracheobronchial epithelial cells. 112 Fujisawa et al 113 suggested that IL-17A is able to promote MUC5AC secretion through its effects on NF-κB-based transcriptional mechanisms in airway epithelial cells. Later, Xia et al 114 demonstrated that IL-17A can also induce MUC5AC expression via the Act1-mediated signaling pathway by interfering with siRNA.…”

“…114 (5, 6) IL-17 can directly or indirectly (via IL-6) activate the ERK1/2 signaling pathway to induce MUC5B secretion. 111,112 (7) IL-22 can induce MUCI secretion by activating JAK1/STAT3 signaling pathway. 126,127 MUC1 (a membrane-bound mucin located on the nasal mucosa) in nasal polyp tissues via an IL-22R1 dependent pathway (Figure 3).…”

“… 114 (5, 6) IL‐17 can directly or indirectly (via IL‐6) activate the ERK1/2 signaling pathway to induce MUC5B secretion. 111 , 112 (7) IL‐22 can induce MUCI secretion by activating JAK1/STAT3 signaling pathway. 126 , 127 …”

Paradoxical psoriasis with IL-17 inhibitors

“…[ 2 ] reported that the incidence rate of paradoxical PsO in patients with inflammatory bowel disease was 5/100 person-years and that smoking is the main risk factor for developing these lesions. In addition to TNF-α, several proinflammatory cytokines such as IL-1β, IL-6, IL-8 and IL-17 are implicated in the pathogenesis of autoimmune diseases that fall under the umbrella of spondyloarthritis [ 3 ]. Karamanakos et al .…”