The clinical phenotype of
psoriasis results from infiltration of T cells in the skin and elaboration of inflammatory
cytokines.
Interleukin (IL)-12 and, more recently,
IL-23 have been implicated in the pathogenesis of psoriatic lesions. New
therapies, including a
monoclonal antibody against a subunit shared by
IL-12 and
IL-23, have been developed to treat
psoriasis. Our purpose was to review the literature on
IL-12 and
IL-23 as a basis for understanding the use of anti-
IL-12/IL-23
therapy for
psoriasis. A review of English-language articles was performed using PubMed to identify articles pertaining to
IL-12,
IL-23, and
psoriasis.
IL-12 and
IL-23 share a common subunit (p40) and have a distinct subunit (p35 and p19, respectively). Transgenic mice that overexpress
IL-12 p40 develop inflammatory skin lesions. Both
IL-12 knockout mice, which are deficient in
IL-12, and human beings with a genetic
IL-12 deficiency show increased susceptibility to intracellular pathogens and defective delayed-type
hypersensitivity responses. These genetic deficiency states suggest the potential for adverse side effects from clinical administration of anti
IL-12 p40
therapy.
IL-12 p40 antibody was well tolerated in a phase I clinical trial with few adverse events and substantial improvements in
psoriasis in most individuals. There was dose-dependent efficacy and substantial improvement in a larger cohort of patients in a phase II clinical trial. Larger and longer trials of anti
IL-12/IL-23
therapies are needed to assess their clinical use and potential for
infection and other adverse events.