Rationale and safety of anti-interleukin-23 and anti-interleukin-17A therapy.

PURPOSE OF REVIEW: Interleukin-12 is a heterodimeric cytokine and an important mediator of the cellular immune response. The recent discovery of the novel cytokine interleukin-23 has led to a re-evaluation of interleukin-12 biology, as both cytokines use a common p40 subunit. This review discusses understanding of what distinguishes these related cytokines and the infection risks associated with targeting these cytokine pathways during treatment of inflammatory diseases. RECENT
FINDINGS: Recent work has shown that interleukin-23 stimulates the development of a distinct subset of effector T cells that produce interleukin-17A. These interleukin-17A-producing cells are critical mediators of the inflammatory response in several mouse models of autoimmunity. Although it is well established that interleukin-12 is a critical mediator of host defense, the role of the interleukin-23/interleukin-17A axis during infections has only recently been evaluated.
SUMMARY: Interleukin-12 and interleukin-23 have distinct roles in mediating host defense and autoimmune inflammation. Although targeting interleukin-12 and interleukin-23 simultaneously against the common p40 subunit is efficacious in clinical trials for human autoimmune diseases, targeting of interleukin-23 alone or the downstream effector cytokine interleukin-17A may be an effective treatment strategy for organ-specific autoimmune diseases. It is likely that targeting interleukin-23 or interleukin-17A alone, as opposed to targeting interleukin-12 and interleukin-23 together, will reduce the patients' risk of developing treatment-related infections.