Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis

Abstract

Emerging data in mice and humans reveals a critical contribution of Th17-associated cytokines, particularly interleukin-(IL)-23 and IL-17, in the pathogenesis of psoriasis. The IL-23/Th17 pathway is a therapeutic target for biologic agents and systemic therapies in psoriasis treatment. A literature search was performed to review and summarize the current evidence on IL-17 and IL-23 as a basis for understanding the use of anti-IL-17 and anti-IL-23 agents for psoriasis therapy. Using PubMed, recent articles were identified pertaining to IL-17, IL-23, and psoriasis. Signaling via the heterodimeric IL-23 receptor induces production of IL-17, which stimulates production of proinflammatory keratinocyte cytokines that mediate the psoriatic response. An overexpression of IL-23, IL-17, or Th17 cells in transgenic mice is associated with the development of inflammatory disease. Both IL-17 knockout mice and humans with a genetic IL-17 deficiency are susceptible to extracellular and intracellular pathogens. This suggests a potential for adverse effects from clinical administration of anti IL-23-p40/IL-17 therapies. Anti-p40 antibodies, briakinumab and ustekinumab, were tolerated in clinical trials and substantially improved psoriasis. Further trials of anti IL-17 therapies are needed to assess their clinical use and potential for infection and other adverse events.