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