CRAIG A.ELMETSMDMOLLY A.HINSHAWMDJAY C.KLEMMEMD, MPHMARK R.PITTELKOWMDMARIA L. CHANCOTURNERMDMARTIN A.WEINSTOCKMD, PhDDAVID T.WOODLEYMD
Interleukin-12, Interleukin-23, and Psoriasis: Current Prospects Torti DC, Feldman SR J Am Acad Dermatol. 2007;57(6):1059-1068
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.
Prodanovich S, Shelling ML, Federman DG, Kirsner RS. Cytokine Milieu in Psoriasis and Cardiovascular Disease May Explain the Epidemiological Findings Relating These 2 Diseases. Arch Dermatol. 2008;144(11):1518–1519. doi:10.1001/archderm.144.11.1518
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