IL-17 in Chronic Inflammation: From Discovery to Targeting

Interleukin-17 (IL-17) is a proinflammatory cytokine that plays a key role in host defense against extracellular bacterial and fungal infections. T helper 17 (Th17) cells play a key role in the production of IL-17. Increased production and contribution of IL-17 have been associated with several inflammatory disorders, including psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. The first antibody against IL-17 was approved by the FDA and EMA in 2015 for the treatment of psoriasis. Other IL-17 inhibitors are under development for a growing number of clinical indications. These include bispecific molecules targeting IL-17A and IL-17F as well as tumor necrosis factor (TNF) and IL-17A. Inhibitors of Th17 differentiation include those that target IL-23 and the transcription factor retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt). Interleukin-17 (IL-17) is a cytokine which elicits protection against extracellular bacterial and fungal infections and which plays important roles in inflammation. However, when produced in excess, it contributes to chronic inflammation associated with many inflammatory and autoimmune disorders. This has made IL-17 an attractive therapeutic target. The present review describes the structure of the IL-17 family, the IL-17 receptor complex, and the cells producing IL-17. The contributions of IL-17 to disease as well as new IL-17-based treatment options are discussed. Finally, the results of IL-17 or IL-17 receptor inhibitors in clinical trials are detailed. With a fruitful outlook, drug registration has now been granted for psoriasis psoriatic arthritis and ankylosing spondylitis, and also bears great potential in a growing number of conditions. Interleukin-17 (IL-17) is a cytokine which elicits protection against extracellular bacterial and fungal infections and which plays important roles in inflammation. However, when produced in excess, it contributes to chronic inflammation associated with many inflammatory and autoimmune disorders. This has made IL-17 an attractive therapeutic target. The present review describes the structure of the IL-17 family, the IL-17 receptor complex, and the cells producing IL-17. The contributions of IL-17 to disease as well as new IL-17-based treatment options are discussed. Finally, the results of IL-17 or IL-17 receptor inhibitors in clinical trials are detailed. With a fruitful outlook, drug registration has now been granted for psoriasis psoriatic arthritis and ankylosing spondylitis, and also bears great potential in a growing number of conditions.