The IL-17/IL-23 Axis

The IL-23/IL-17 axis is a central driver of immune-mediated inflammatory disease. IL-23, produced by dendritic cells and macrophages in response to microbial signals and tissue damage, acts as a master regulator — driving the differentiation and survival of Th17 cells. These Th17 cells produce IL-17A and IL-17F, which act on keratinocytes, synoviocytes, and osteoclasts to generate the downstream inflammatory cascade responsible for psoriatic plaques, joint destruction, and enthesitis.Understanding this hierarchy — IL-23 upstream, IL-17 downstream — is clinically important. Blocking upstream (IL-23) tends to produce more durable remission with less frequent dosing. Blocking downstream (IL-17) produces faster initial response. This distinction drives treatment sequencing decisions, particularly in patients with incomplete response to first-line biologics.A critical prescribing consideration: IL-17 blockers are contraindicated or require caution in patients with active inflammatory bowel disease, as IL-17 plays a protective mucosal role in the gut. IL-23 blockers do not carry this restriction — and may in fact have benefit in Crohns disease.