Biologic treatment of crohn's disease: Briakinumab and ustekinumab

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The introduction of IL-12/IL-23 anti-p40 antibodies as a novel therapy for Crohn's disease is a case study in basic immunologic observations derived from animal models of human disease thereby propelling innovative, targeted treatment into the clinic. In this case, IL-12 was initially suggested as the driving force behind the dysregulated immune response in Crohn's disease (IL-23 was discovered ometime later). Based on work from Mosmann and Coffman [1], reactive inflammatory T cell responses were separated into two major types, so-called Th1 T cells that produce interferongamma (IFN g) and Th2 cells that produce IL-4, IL-5, and IL-13. An excess of Th1 cytokine production by lamina propria monocytes and T cells was seen in animal models of Crohn's disease as well as in Crohn's patients [2, 3]. Th1 cells are directly induced by interleukin-12. IL-12 is secreted by antigen-presenting cells activated by particular microbial components; naïve T cells encountering a cognate ligand presented by a monocyte in the presence of IL-12 develop into Th1 cells and secrete IFN g as part of the Th1 inflammatory response after encountering the same ligand thereafter. Interleukin-12 is a heterodimeric protein composed of two covalently bound subunits, a p35 and p40 protein named for their relative molecular sizes (Fig. 34.1). Interleukin-12 binds to a specific cell surface receptor on T cells, the IL-12 receptor, another heterodimeric protein composed of the IL-12 receptor beta 1 (IL12R b 1) and 2 (IL12R b 2) subunits.

Original languageEnglish (US)
Title of host publicationCrohn's Disease and Ulcerative Colitis
Subtitle of host publicationFrom Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach
PublisherSpringer US
Pages433-440
Number of pages8
ISBN (Electronic)9781461409984
ISBN (Print)9781461409977
DOIs
StatePublished - Jan 1 2012

Keywords

  • Briakinumab
  • Interleukin-12
  • Interleukin-23
  • Ustekinumab

ASJC Scopus subject areas

  • Medicine(all)

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