title: IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases.
abstract: The cytokine interleukin-12 (IL-12) was thought to have a central role in T cell-mediated responses in inflammation for more than a decade after it was first identified. Discovery of the cytokine IL-23, which shares a common p40 subunit with IL-12, prompted efforts to clarify the relative contribution of these two cytokines in immune regulation. Ustekinumab, a therapeutic agent targeting both cytokines, was recently approved to treat psoriasis and psoriatic arthritis, and related agents are in clinical testing for a variety of inflammatory disorders. Here we discuss the therapeutic rationale for targeting these cytokines, the unintended consequences for host defense and tumor surveillance and potential ways in which these therapies can be applied to treat additional immune disorders.
authors.affiliation: 1] Cancer Immunoregulation and Immunotherapy and Immunology in Cancer and Infection Laboratories, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. [2] School of Medicine, University of Queensland, Herston, Queensland, Australia.
authors.forename: Michele W L
authors.identifier: 0000000318869145
authors.initials: MW
authors.lastname: Teng
authors.affiliation: Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Bowman
authors.affiliation: Merck Research Laboratories, Boston, Massachusetts, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: McElwee
authors.affiliation: 1] Cancer Immunoregulation and Immunotherapy and Immunology in Cancer and Infection Laboratories, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. [2] School of Medicine, University of Queensland, Herston, Queensland, Australia.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.affiliation: 1] St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA. [2] Howard Hughes Medical Institute, New York, New York, USA. [3] Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Paris, France. [4] Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, Paris, France. [5] Paris Descartes University, Imagine Institute, Paris, France.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Trudeau Institute, Inc., Saranac Lake, New York, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cooper
authors.affiliation: Merck Research Laboratories, Palo Alto, California, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
mesh_terms: D000818:Animals; D006801:Humans; D007109:Immunity; D007157:Immunologic Surveillance; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058990:Molecular Targeted Therapy
chemical_list: D053759:Interleukin-23; D018664:Interleukin-12