Interleukin-12, interleukin-23, and psoriasis: Current prospects - 19/08/11
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.
Le texte complet de cet article est disponible en PDF.Abbreviations used : IFN, IL, mRNA, Th1
Plan
Funding sources: The Center for Dermatology Research is funded by a grant from Galderma Laboratories LP. |
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Conflicts of interest: None declared. |
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Reprints not available from the authors. |
Vol 57 - N° 6
P. 1059-1068 - décembre 2007 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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