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Inflammation bowel disease II
TH1/TH17 profiles in crohn's disease: a cross sectional single centre study in postoperative crohn's disease
  1. A U Murugananthan *1,
  2. D Bernardo1,
  3. P Tozer1,
  4. C T Tee1,
  5. E Mann1,
  6. A L Hart2,
  7. N Arebi2,
  8. S C Knight1,
  9. H O Al-Hassi1
  1. 1Antigen Presentation Research Group, Imperial College, London, UK
  2. 2Gastroenterology, St Mark's Hospital, London, UK

Abstract

Introduction Th1 and Th17 pathways are implicated in Crohn's disease (CD). In operative resection samples healthy ileum shows high TGFβ levels in patients who develop recurrence, with TGFβ being a known activator of the Th17 response. Other studies in CD show a dominant Th1 cytokine profile, with high levels of IFNγ, which reduce Th17 response and augment Th1 response. The relationship of Th1/Th17 cytokine profiles in postoperative CD has not been examined. The authors aimed to study tissue Th1/Th17 cytokine secretion after in vitro biopsy culture in postoperative CD.

Methods Colonoscopy was undertaken in postoperative CD patients. Recurrence graded as no/minimal inflammation (Rutgeert Score (RS) ≥1) or progressive inflammation (RS≥2). Ileal biopsies were cultured overnight and cell free supernatants obtained. Supernatant cytokines (IL-2, IL-4, IL-10, IL-17 TNFα, INFg and IL-6) were assessed by flow cytometry using cytometric bead array (Becton Dickinson). Statistical analysis was via unpaired t tests.

Results Consecutive patients attending endoscopy (n=24, 9M/15F) were identified. Mean age 45.0 years and time from I to C resection was 5.8 years; 5 patients were smokers. Drugs were thiopurines 13, Infliximab 1 and nil 10. Endoscopic severity was i0 n=5, i1 n=6, i2 n=5, i3 n=3, i4 n=5. Mean cytokine concentrations from supernatants are shown in the table 1. Comparison between RS≥1 and ≥2 showed that pro-inflammatory cytokines IL-17a (p<0.02) and IFNγ (p<0.03) were significantly higher in RS i2-i4 neo terminal ileum as compared with those with RS i0-i1. The regulatory cytokine IL-10 was significantly higher in patients with RS≥1 (p<0.038).

Table 1

PTH-046

Conclusion Cytokine profiles in those with RS≥2, show higher levels of IL-17a and IFNγ and reduced IL-10 compared to RS≥1. This profile supports a Th17 and Th1 mediated response as one of the early instigators of endoscopic progression in postoperative CD. The authors' observation is consistent with recent findings of a T cell subset able to produce cytokines involved in both Th1 and Th17 responses. Previous therapies directed at Th1 pathway, for example, anti-IL-12p40 antibody ustekinumab and anti-IFNγ Fontolizumab failed to show significant clinical benefit in CD. Given our findings targeting the Th17 response, for example, with anti-IL-23 antibodies and anti-IL-17 may deliver improved therapeutic outcome.

  • cytokines
  • postoperative Crohn's disease
  • TH1/TH17.

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Footnotes

  • Competing interests None.

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