HPE 91 – March 2019 | Page 29

REVIEW Interleukins in moderate to severe psoriasis Cytokines, particularly interleukin-17 (IL-17) and IL-23, appear to play a pivotal role in the development of psoriasis and much effort has been placed on the development of drug that specifically target them Rod Tucker BPharm PhD Robert Gordon University, Aberdeen, UK SCIENCE PHOTO LIBRARY It is widely recognised that psoriasis is more than just a skin condition and is best described as a systemic, immune-mediated disease that causes chronic inflammatory changes in the skin. It is estimated to affect between 2% and 4% of the population in Westernised countries and the prevalence is greater in areas further north and south of the equator. 1 Although originally considered to be primarily due to a disorder of keratinocytes, its successful treatment with immune-suppressive drugs such as ciclosporin led to a suggestion that psoriasis is an immune-mediated disorder. It is now acknowledged that psoriasis results from a complex interplay between genetics, environmental factors and the host’s immune system. This interaction ultimately results in the proliferation of abnormal keratinocytes in the skin and the formation of the characteristic silvery, white plaques of psoriasis seen on extensor surfaces such as the elbows and knees. Over the last 15 years, the introduction of biologic drugs has revolutionised the management of patients with moderate to severe psoriasis. These drugs target various immune-related cytokines and in recent years, attention has focused on two particular cytokines: interleukin 23 (IL-23) and interleukin 17 (IL-17). These appear to play a pivotal role in the development of the disease and much effort has been placed on the development of drugs that specifically target them. The latest biologic drug to receive regulatory approval is tildrakizumab, which targets IL-23. The role of cytokines in psoriasis Cytokines have an important role linking the innate and adaptive immune systems. In response to pathogens, innate immune cells (that is, activated antigen presenting cells such as dendritic cells and macrophages) secrete cytokines that then instruct naïve T cells to differentiate into various sub-types that kill the invading pathogens. IL-12 is a family of four members (IL-12, IL-23, IL-27 and IL-35) that is also involved in regulation of several pathways related to proper immune system functioning. For example, IL-12 instructs naïve T cells to change into T1 helper cells (Th 1), which then fight infections. IL-12 also has a role in inflammatory diseases and levels are increased (as are Th 1 cells) in rheumatoid arthritis and various autoimmune diseases such as multiple sclerosis. IL-23 was discovered in 2000 and likewise appears to have an important role in inflammatory diseases. In psoriasis, IL-23 activates naïve T cells to hospitalpharmacyeurope.com | 2019 | Issue 91 | 29