Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice

Gastroenterology. 2007 Jun;132(7):2359-70. doi: 10.1053/j.gastro.2007.03.104. Epub 2007 Apr 13.


Background & aims: Interleukin (IL)-23 supports a distinct lineage of T cells producing IL-17 (Th17) that can mediate chronic inflammation. This study was performed to define the role of IL-23 and Th17 cells in chronic colitis in mice.

Methods: Colitis was induced by transfer of a cecal bacterial antigen-specific C3H/HeJBir (C3Bir) CD4(+) T-cell line to C3H/HeSnJ SCID mice. Cytokines were measured by flow cytometry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. Monoclonal anti-IL-23p19 was administered at the same time as or 4 weeks after pathogenic CD4 T-cell transfer. A histopathology colitis score was assessed in a blinded fashion.

Results: The pathogenic C3Bir CD4(+) T-cell line contained more cells producing IL-17 than those producing interferon-gamma and these were distinct subsets; after adoptive transfer to SCID recipients, Th17 cells were predominant in the lamina propria of mice with colitis. Bacteria-reactive CD4(+) Th1 and Th17 lines were generated. The Th17 cells induced marked inflammation in a dose-dependent manner. Even at a dose as low as 10(4) cells/mouse, Th17 cells induced more severe disease than Th1 cells did at 10(6) cells/mouse. Monoclonal anti-IL-23p19 prevented and treated active colitis, with down-regulation of a broad array of inflammatory cytokines and chemokines in the colon. Anti-IL-23p19 induced apoptosis in colitogenic Th17 cells in vitro and in vivo.

Conclusions: Bacterial-reactive CD4(+) Th17 cells are potent effector cells in chronic colitis. Inhibition of IL-23p19 was effective in both prevention and treatment of active colitis. IL-23 is an attractive therapeutic target for inflammatory bowel disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cecum / microbiology
  • Cell Line
  • Colitis / drug therapy
  • Colitis / immunology
  • Colitis / physiopathology*
  • Colitis / prevention & control
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-23 / biosynthesis
  • Interleukin-23 / immunology*
  • Interleukin-23 / metabolism
  • Interleukin-23 Subunit p19 / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, SCID
  • T-Lymphocyte Subsets / metabolism


  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • Interleukin-17
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukin-12
  • Interferon-gamma