The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23 functions and abrogates IL-23-mediated antitumour effects

Immunology. 2006 Jan;117(1):22-8. doi: 10.1111/j.1365-2567.2005.02257.x.


Interleukin (IL)-23 is a heterodimeric cytokine consisting of a novel p19 molecule and the p40 subunit of IL-12. Since secreted p40 can act as an antagonist for IL-12, we investigated whether p40 also inhibited IL-23-mediated immunological functions. p40 did not induce interferon (IFN)-gamma or IL-17 production from splenocytes but impaired IL-23-induced cytokine production by competitive binding to the IL-23 receptors. Furthermore, a mixed population of murine colon carcinoma Colon 26 cells transduced with the p40 gene and those transduced with the IL-23 gene developed tumours in syngenic mice, whereas the IL-23-expressing Colon 26 cells were completely rejected. p40 also suppressed IFN-gamma production of antigen-stimulated splenocytes and IL-23-mediated cytotoxic T-lymphocyte activities in the mice that rejected Colon 26 cells expressing IL-23. p40 can thereby antagonize IL-23 and is a possible therapeutic agent for suppression of IL-23 functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / prevention & control
  • Cytokines / biosynthesis
  • Cytotoxicity, Immunologic / immunology
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology*
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / antagonists & inhibitors*
  • Interleukins / genetics
  • Interleukins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Protein Subunits / genetics
  • Protein Subunits / immunology*
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Transduction, Genetic
  • Tumor Cells, Cultured


  • Cytokines
  • Il23a protein, mouse
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Protein Subunits
  • Interleukin-12
  • Interferon-gamma