title: Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis.
abstract: Emerging data in mice and humans reveals a critical contribution of Th17-associated cytokines, particularly interleukin-(IL)-23 and IL-17, in the pathogenesis of psoriasis. The IL-23/Th17 pathway is a therapeutic target for biologic agents and systemic therapies in psoriasis treatment. A literature search was performed to review and summarize the current evidence on IL-17 and IL-23 as a basis for understanding the use of anti-IL-17 and anti-IL-23 agents for psoriasis therapy. Using PubMed, recent articles were identified pertaining to IL-17, IL-23, and psoriasis. Signaling via the heterodimeric IL-23 receptor induces production of IL-17, which stimulates production of proinflammatory keratinocyte cytokines that mediate the psoriatic response. An overexpression of IL-23, IL-17, or Th17 cells in transgenic mice is associated with the development of inflammatory disease. Both IL-17 knockout mice and humans with a genetic IL-17 deficiency are susceptible to extracellular and intracellular pathogens. This suggests a potential for adverse effects from clinical administration of anti IL-23-p40/IL-17 therapies. Anti-p40 antibodies, briakinumab and ustekinumab, were tolerated in clinical trials and substantially improved psoriasis. Further trials of anti IL-17 therapies are needed to assess their clinical use and potential for infection and other adverse events.
authors.affiliation: Department of Dermatology, Center for Dermatology Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Parvathi
authors.initials: P
authors.lastname: Mudigonda
authors.forename: Tejaswi
authors.initials: T
authors.lastname: Mudigonda
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Feneran
authors.forename: Habibollah S
authors.initials: HS
authors.lastname: Alamdari
authors.forename: Laura
authors.initials: L
authors.lastname: Sandoval
authors.forename: Steven R
authors.initials: SR
authors.lastname: Feldman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000627:therapeutic use*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D053759:Interleukin-23 / Q000378:metabolism / Q000502:physiology*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D058504:Th17 Cells / Q000378:metabolism / Q000502:physiology*; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D020381:Interleukin-17; D053759:Interleukin-23; C544528:briakinumab; D000069549:Ustekinumab