Interleukin-12, interleukin-23, and Psoriasis: Current Prospects

J Am Acad Dermatol. 2007 Dec;57(6):1059-68. doi: 10.1016/j.jaad.2007.07.016. Epub 2007 Aug 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Infections / prevention & control
  • Clinical Trials as Topic
  • Cryptococcosis / drug therapy
  • Humans
  • Interleukin-12 / immunology
  • Interleukin-12 / physiology*
  • Interleukin-12 Subunit p40 / deficiency
  • Interleukin-12 Subunit p40 / immunology
  • Interleukin-12 Subunit p40 / physiology*
  • Interleukin-23 / immunology
  • Interleukin-23 / physiology*
  • Leishmaniasis / prevention & control
  • Mice
  • Mice, Knockout
  • Psoriasis / drug therapy*
  • Psoriasis / etiology
  • Psoriasis / immunology
  • Receptors, Interleukin-12 / deficiency
  • Toxoplasmosis, Animal / prevention & control
  • Virus Diseases / prevention & control

Substances

  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Receptors, Interleukin-12
  • Interleukin-12