The role of interleukin-17A in psoriatic disease.

Abstract

The pathogenic mechanisms of specific immune-mediated inflammatory diseases (IMIDs) are not fully understood, but are thought to involve activated T cells with the release of pro-inflammatory cytokines. Understanding the autoimmune inflammatory pathways has led to the development of biological agents that target specific components of effector immune mechanisms. Despite the availability of many effective drugs, a large proportion of patients with moderate to severe IMID do not receive adequate treatment, and many therapies show decreased efficacy over time. Therefore, there is a need for new therapies. One subset of T helper cells, Th17, and the cytokine interleukin-17 (IL-17) play a central role in the pathophysiology of autoimmune diseases such as psoriasis. IL-17 is involved in the modulation of pro-inflammatory cytokines, haematopoietic growth factors, antimicrobial peptides, chemokines, and molecules involved in tissue remodelling; the inflammatory cascades triggered by Th17 cells and IL-17 itself, when unregulated, can result in widespread inflammation-related damage. Evidence of increased Th17 activity and high levels of IL-17 has been found in psoriasis, as well as other inflammatory conditions, thereby signalling the potential utility of IL-17 as a therapeutic target. Clinical trials investigating IL-17 inhibitors, such as secukinumab, in patients with psoriatic disease have reported no significant safety concerns so far. It is hoped that these agents will improve the long-term prognosis of patients with these debilitating disorders.