Our immune system is a complex network and relies on communication molecules to carry out its functions. The big group of communication molecules are called cytokines. They deliver messages to the immune system which signal certain actions like further cytokine production or recruitment of additional immune cells.
Interleukin-17 (IL-17) is a proinflammatory family of cytokines classically produced by immune cells called T helper Th17 lymphocytes and driven by interleukin-23 (IL-23) or interleukin-1β (IL-1β). IL-17 is a cytokine family that plays an important role in immune function. There are six members of the IL-17 family, A, B, C, D, E, F. The IL-17 family is responsible for the development of the adaptive immune response which includes neutrophil recruitment and release of chemokines and antimicrobial peptides to defend barrier tissues against, yes, those pesky pathogens that like to make us sick.
When IL-17 is overproduced, it contributes to chronic inflammation and tissue damage. In autoimmune conditions like psoriasis and hidradenitis suppurativa (HS), IL-17 plays an important role in their pathogenesis. For psoriasis, IL-17 triggers keratinocytes to divide at an accelerated rate, which results in the thick, raised, and scaly plaques characteristic of the disease. IL-17 acts as a calling card. It forces keratinocytes to secrete pro-inflammatory proteins which recruit immune cells—especially neutrophils and more T-cells—directly into the skin lesion. This creates a vicious cycle of inflammation and IL-17 production. Similar to psoriasis, IL-17 in hidradenitis suppurativa also drives neutrophils, keratinocyte proliferation and a loop of constant inflammation. Antimicrobial peptides are also increased. One difference between psoriasis and HS is HS-derived Th17 cells produce significantly higher levels of IL-17F. In addition, the IL-1β pathway appears to be a main driver of IL-17 production rather than IL-23.
Because of the role IL-17 plays in HS and psoriasis, it has become a therapeutic target. Known as IL-17 inhibitors, these drugs target either IL-17A, IL-F or the IL-17 receptor to stop the inflammatory response. Currently there are four IL-17 inhibitors FDA approved.
- Secukinumab (Cosyntex): IL-17A inhibitor approved for moderate-to-severe plaque psoriasis. It is additionally approved for psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, enthesitis-related arthritis, and hidradenitis suppurativa.
- Ixekizumab (Taltz): IL-17A inhibitor approved for plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis.
- Brodalumab (Siliq): IL-17 receptor antagonist approved for moderate to severe plaque psoriasis.
- Bimekizumab (Bimzelx): IL-17A and IL-17F inhibitor. Currently approved for plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, and hidradenitis suppurativa.
The IL-17 inhibitors vary with dosing schedule, loading dose, binding affinity, and half-life, which may play a role when choosing which therapy is best aligned with a patient’s preference or clinical need. If one does not work well for a patient, then switching within class is a reasonable change and could yield better results.
Trotter’s Take: IL-17 plays an important role in the pathogenesis of psoriasis and hidradenitis suppurativa and they are a powerful tool to treat these conditions.
Want to know more about what makes the IL-17 therapies unique? Then check out my latest podcast with Dr. Naiem Issa as he explains the IL-17 inhibitors.
