P049. A possible role of mucosal cytokine profile for predicting response to infliximab therapy in ulcerative colitis
R. Rismo1, T. Olsen1, G. Cui2, I. Christiansen2, J. Florholmen1, R. Goll1
1Laboratory of Gastroenterology, Institute of Clinical medicine, University of Tromsoe, Department of gastroenterology, University Hospital North Norway, Tromsoe, Norway; 2Laboratory of Gastroenterology, Institute of Clinical medicine, University of Tromsoe, Tromsoe, Norway
Background: Mucosal cytokine profile determines T cell differentiation and may play an important role in the clinical course of inflammatory bowel disease. Ulcerative colitis (UC) was previously considered a Thelper (Th)2 driven disease. However, Th17 as well as Th1 and regulatory T cell related cytokines are elevated in inflamed mucosa of patients with ulcerative colitis. Treatment with infliximab (IFX), an anti-TNF-alpha agent, is effective in inducing remission in patients with moderate to severe UC, but few studies exist on the predictive value of mucosal markers in the treatment. The aim of this study was to characterize the pre-treatment mucosal cytokine profile and assess its possible predictive value for the response to IFX therapy.
Methods: We quantified the expression of Th1, Th17, Th2 and Treg related cytokines in inflamed mucosal biopsies from UC patients before initiation of IFX induction therapy by real-time PCR, and assessed the clinical and endoscopic effect after 3 infusions. Remission was defined by UCDAI less than 3. Univariate and multivariate logistic regression analyses were used to assess the possible predictive values of cytokines and transcription factors associated with the different T cell lines.
Results: Seventy-four patients were included. 43 (58%) were in remission and 31 (42%) in non-remission after 3 infusions of IFX. No clinical or demographical characteristics were significantly different between patients in remission and non-remission. There were significantly higher pre-treatment mucosal mRNA expression levels of IL‑17A and IFN-gamma in patients achieving remission compared to non-remission (p = 0.005 and p = 0.003, respectively). High expression of IL‑17A and IFN-gamma was significantly associated with remission after 3 infusions of IFX (p = 0.013, OR = 5.4 and p = 0.011, OR = 5.5, respectively). Treg and Th2 related cytokines did not predict remission. IL‑17A mRNA expression correlated positively with IFN-gamma mRNA and foxp3 mRNA expression, but not with the Th2 transcription factor GATA3.
Conclusions: The expression of Th1 and Th17 related cytokines, but not Treg or Th2 related cytokines in the mucosa of UC patients, can potentially predict the effect of induction therapy of IFX.