Interleukin-12, interleukin-23, and psoriasis: current prospects.

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.

• Authors: Dorothea C Torti, Steven R Feldman
• Journal: Journal of the American Academy of Dermatology (J Am Acad Dermatol) Vol. 57 Issue 6 Pg. 1059-68 (Dec 2007) ISSN: 1097-6787 [Electronic] United States
• PMID: 17706835 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

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

Topics

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