Late Crohn's disease patients present an increase in peripheral Th17 cells and cytokine production compared with early patients

Aliment Pharmacol Ther. 2010 Mar;31(5):561-72. doi: 10.1111/j.1365-2036.2009.04209.x. Epub 2009 Dec 3.


Background: Th1 and Th17 cells have been implicated in Crohn's disease (CD) pathophysiology and may play a role in disease persistence. Aim To determine Th1 and Th17 responses in intestine and peripheral blood of early (<32 weeks since initial symptoms) and late (>2 years) CD patients.

Methods: Cytokine mRNA in intestinal biopsies was determined by RT-PCR. Cytokine concentration in culture was measured by ELISA and cytokine-producing cells were identified by intracellular staining.

Results: The inflamed mucosa showed significantly increased IL-17 mRNA levels compared with non-inflamed areas, both in early and late CD patients. However, only patients with late (n = 12), but not early (n = 9), active disease showed increased IL-17 production, as well as a significantly higher percentage of IL-17(+)CD4(+) cells in blood, compared with controls (n = 12) or patients in remission (n = 13). Moreover, cultured peripheral CD4(+) cells from late active CD patients presented significantly higher percentages of IL-17(+), IL-22(+) and IFN-gamma(+) and a significantly increased production of IL-17 and IL-22, but not IFN-gamma(+).

Conclusions: Increased IL-17 gene transcription is common to early and late CD mucosa. However, exacerbated Th17 responses in the peripheral blood appear only in late disease. We propose that this population may constitute a mechanism of perpetuating the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • CD4-Positive T-Lymphocytes / immunology*
  • Crohn Disease / blood
  • Crohn Disease / immunology*
  • Cytokines / blood
  • Cytokines / immunology*
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunologic Memory
  • Inflammation / immunology
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / blood
  • Interleukin-17 / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th1 Cells / immunology
  • Transcription, Genetic
  • Young Adult


  • Cytokines
  • Interleukin-17
  • RNA, Messenger