S1713 IL-12/IL-23 P40 Peptide-Based Vaccine Ameliorates TNBS-Induced Murine Chronic Colitis By Down-Regulation of TH1 and TH17 Cytokines

Abstract

BACKGROUND: The aetiology of crohn's disease (CD) is poorly understood at present, but an immune pathology involving the CD4+T-cell phenotypes is suspected to be a major factor for the development and the perpetuation of CD. In line with this thinking, recently, we found that in patients with ulcerative colitis, the peripheral level of the regulatory CD4+CD25High+ T-cell phenotype was compromised, while the CD4+ T-cells lacking CD28 (CD4+CD28-) had expanded (Dig Dis Sci 2007;52:2725-31). We have now extended our work to patients with CD. METHODS: The study subjects included 31 patients with active CD (aCD) who were to be treated with infliximab (IFX). At baseline, the mean values of CD activity index (CDAI) and the duration of CD were 200.9±84.8 and 5.7±7.0 years, respectively. Sixteen patients with CD in remission (rCD, CDAI≤150) and 19 healthy control (HC) subjects were also included in this study. Fifteen patients received IFX as initial (top down) therapy, 7 received IFX as an episodic (step up) therapy, and the other 9 received IFX after operation. Peripheral blood samples were obtained before and 12 hours after each IFX infusion. Lymphocytes were stained with anti CD4, anti CD25 and anti CD28 antibodies for analyses by fluorescence-activated cell sorter (FACS) in flow cytometry. RESULTS: The aCD group had significantly lower level of CD4+CD25High+ T-cell expression as compared with the rCD group (P<0.05) or the HC group (P<0.05). A significant up-regulation of CD4+CD25High+ T-cell phenotype was associated with the post first IFX infusion as compared with the pre first IFX infusion (P<0.01). Conversely, patients with aCD had higher % CD4+CD28T-cells as compared with the rCD group (P<0.05) or the HC group (P<0.05). A significant down-modulation of the CD4+CD28T-cell phenotype was associated with post first IFX infusion vs pre first IFX infusion (P<0.01) CONDLUSIONS: IFX therapy was associated with a marked improvement of patients' quality of life, but our clinical observations indicated that the efficacy of IFX diminishes after frequently administration. However, in this study, the clinical efficacy of IFX was associated with a significant up modulation of the regulatory CD4+CD25High+ T-cell phenotype and unexpectedly, some normalization of peripheral CD4+CD28T-cell phenotype. We believe that a likely impact of IFX on key cells of the immune system is potentially very significant and warrants to be substantiated in future studies.