Interleukin-25 inhibits interleukin-12 production and Th1 cell-driven inflammation in the gut

Gastroenterology. 2009 Jun;136(7):2270-9. doi: 10.1053/j.gastro.2009.02.049.


Background & aims: During the pathogenesis of Crohn's disease (CD), interleukin (IL)-12, a cytokine produced by mucosal CD14+ monocyte-like cells, promotes tissue-damaging T helper cell (Th) 1-mediated inflammation through mechanisms that are not fully understood. IL-25 promotes Th2 cell responses by activating major histocompatibility complex class II-positive non-T and non-B cells. Because Th1 and Th2 cells, and the cytokines they release, are often mutually antagonistic, we examined whether IL-25 affects IL-12 production or Th1 cell-mediated inflammation in the gut.

Methods: Studies were performed using colonic samples from patients and mice with peptidoglycan (PGN)-, 2,4,6-trinitrobenzenesulphonic acid (TNBS)-, or oxazolone-induced colitis. IL-25 receptor (IL-25R) levels were evaluated in intestinal lamina propria mononuclear cells by flow cytometry, and IL-25 levels were measured by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. Mucosal CD14+ cells from patients with CD were incubated with IL-25 and/or lipopolysaccharide or PGN. Mice were injected with IL-25, and some mice first received injections of an IL-13 blocking antibody. Cytokines were quantified by real-time polymerase chain reaction and enzyme-linked immunosorbent assay.

Results: CD14+ cells from the mucosa of CD patients expressed IL-25R and responded to IL-25 by decreasing the synthesis of IL-12 and IL-23. IL-25 prevented PGN-induced colitis in mice. IL-25 induced IL-13 production in the colon, but IL-13 was not required for suppression of PGN colitis. IL-25 ameliorated TNBS- and oxazolone-colitis. Patients with CD or ulcerative colitis produced significantly less IL-25 compared with controls.

Conclusions: IL-25 inhibits CD14+ cell-derived cytokines and experimental colitis. IL-25 could be a useful treatment of CD and ulcerative colitis.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Crohn Disease / immunology
  • Crohn Disease / pathology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Inflammation Mediators / analysis
  • Interleukin-12 / biosynthesis*
  • Interleukin-17 / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Mice
  • Mice, Inbred BALB C
  • Probability
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Th1 Cells / immunology*
  • Th1 Cells / physiology


  • Cytokines
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-12