TH1/TH17 profiles in crohn's disease: a cross sectional single centre study in postoperative crohn's disease: Table 1

Abstract

Rationale and Aims: Th1 and Th17 pathways have been implicated in Crohn's disease (CD). Within postoperative resection samples healthy ileum shows high TGFβ levels in patients who subsequently develop recurrence [1], with TGFβ being a known activator of the Th17 response. Other studies show CD to be dominated by a Th1 cytokine profile, with high levels of IFNγ [2], which reduce the Th17 and augment the Th1 responses. Th1/Th17 responses in postoperative CD have not been examined. We 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]≤i1) or progressive inflammation (RS≥i2). Ileal biopsies were cultured overnight and cell free supernatants obtained. Cytokines (IL-2, IL-4, IL10, IL17 TNF α, IFNγ and IL6) were assessed in the supernatants 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 over a 1-year period. Mean age 45.0 yrs and time from I-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 below. (Table presented) Comparison between RS≥1 and ≥2 showed that proinflammatory cytokines IL17a (p < 0.02) and IFNγ (p < 0.03) were significantly higher in RS i2-i4 neo terminal ileum as compared with RS i0 i1. The regulatory cytokine IL-10 was significantly higher in patients with RS≥1 (p< 0.038). Conclusions: Cytokine profiles in the group with RS≥2, show higher levels of IL 17a and IFNγ and reduced IL10 compared to RS≥1. This profile supports the Th17 and Th1 mediated response as one of the early instigators of endoscopic progression in postoperative CD. Our observation is consistent with findings of a T cell subset capable of producing cytokines involved in both Th1 and Th17 responses [3]. Previous therapies directed at Th1 pathway e.g. anti-IL-12p40 antibody ustekinumab and anti-IFNγ Fontolizumab failed to show significant clinical benefit in CD. Given our findings, targeting the Th17 pathway e.g. with anti-IL-23 antibodies and anti-IL17 may deliver an improved therapeutic outcome.