Interleukin-17: A pleiotropic cytokine implicated in inflammatory, infectious, and malignant disorders
Anushka Saran, Daisuke Nishizaki, Scott M. Lippman, Shumei Kato, Razelle Kurzrock
Abstract
IL-17A, referred to as IL-17, is the founding member of a family of pro-inflammatory cytokines, including IL-17B, IL-17C, IL-17D, IL-17E (or IL-25), and IL-17F, which act via receptors IL-17RA to IL-17RE, and elicit potent cellular responses that impact diverse diseases. IL-17’s interactions with various cytokines include forming a heterodimer with IL-17F and being stimulated by IL-23’s activation of Th17 cells, which can lead to inflammation and autoimmunity. IL-17 is implicated in infectious diseases and inflammatory disorders such as rheumatoid arthritis and psoriasis, promoting neutrophil recruitment and anti-bacterial immunity, but potentially exacerbating fungal and viral infections, revealing its dual role as protective and pathologic. IL-17 is also involved in various cancers, including breast, colon, cervical, prostate, and skin cancer, contributing to proliferation, immune invasion, and metastases, but also playing a protective role in certain instances. Four FDA-approved drugs—secukinumab (for ankylosing spondylitis, enthesitis-related arthritis, hidradenitis suppurativa, non-radiographic axial spondyloarthritis, plaque psoriasis, and psoriatic arthritis), ixekizumab (for ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis, and psoriatic arthritis), brodalumab (for plaque psoriasis), and bimekizumab (for plaque psoriasis)—suppress the IL-17 pathway, with more in development, including netakimab, sonelokimab, izokibep, and CJM112. These agents and others are being studied across a spectrum of disorders. Understanding the complicated interplay between IL-17 and other immune mediators may yield new treatments for inflammatory/autoimmune conditions and malignancies. • IL-17A (IL-17) has both protective and pathogenic roles in human diseases. • IL-17 signals through the IL-17RA/IL-17RC receptor complex. • IL-17 promotes infectious immunity, while also contributing to inflammation. • IL-17 has both anti-tumor and pro-tumor properties. • FDA-approved IL-17 antibodies: secukinumab, ixekizumab, brodalumab, bimekizumab.