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Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain.

Interleukin-12 (IL-12) is a heterodimeric molecule composed of p35 and p40 subunits. Analyses in vitro have defined IL-12 as an important factor for the differentiation of naive T cells into T-helper type 1 CD4+ lymphocytes secreting interferon-gamma (refs 1, 2). Similarly, numerous studies have concluded that IL-12 is essential for T-cell-dependent immune and inflammatory responses in vivo, primarily through the use of IL-12 p40 gene-targeted mice and neutralizing antibodies against p40. The cytokine IL-23, which comprises the p40 subunit of IL-12 but a different p19 subunit, is produced predominantly by macrophages and dendritic cells, and shows activity on memory T cells. Evidence from studies of IL-23 receptor expression and IL-23 overexpression in transgenic mice suggest, however, that IL-23 may also affect macrophage function directly. Here we show, by using gene-targeted mice lacking only IL-23 and cytokine replacement studies, that the perceived central role for IL-12 in autoimmune inflammation, specifically in the brain, has been misinterpreted and that IL-23, and not IL-12, is the critical factor in this response. In addition, we show that IL-23, unlike IL-12, acts more broadly as an end-stage effector cytokine through direct actions on macrophages.

Pubmed ID: 12610626


  • Cua DJ
  • Sherlock J
  • Chen Y
  • Murphy CA
  • Joyce B
  • Seymour B
  • Lucian L
  • To W
  • Kwan S
  • Churakova T
  • Zurawski S
  • Wiekowski M
  • Lira SA
  • Gorman D
  • Kastelein RA
  • Sedgwick JD



Publication Data

February 13, 2003

Associated Grants


Mesh Terms

  • Animals
  • Autoimmune Diseases of the Nervous System
  • Brain
  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Deletion
  • Gene Expression Regulation
  • Inflammation
  • Interleukin-1
  • Interleukin-12
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Macrophages
  • Mice
  • Mice, Knockout
  • Protein Subunits
  • RNA, Messenger
  • Th1 Cells
  • Tumor Necrosis Factor-alpha