Efficacy of budesonide therapy in the early phase of treatment of adult coeliac disease patients with malabsorption: An in vivo/in vitro pilot study

C. Ciacci, L. Maiuri, I. Russo, R. Tortora, C. Bucci, C. Cappello, A. Santonicola, A. Luciani, V. Passananti, P. Iovino

Research output: Contribution to journalArticlepeer-review

Abstract

Budesonide is a glucocorticosteroid with a local anti-inflammatory effect. Coeliac disease is an immune-mediated disease caused by gluten ingestion in intolerant patients. The aim of the present study was to investigate the efficacy of budesonide in malabsorptive coeliac patients and its effect in an in vitro gliadin challenge. Twenty coeliac patients with malabsorption were enrolled in the present study and were randomly assigned to one of two 4 week treatments: (i) a gluten-free diet alone; or (ii) a gluten-free diet plus 6 mg budesonide daily. At the end of 4 weeks treatment, all patients underwent clinical evaluation, laboratory tests and self-evaluation of well-being using a visual analogue scale. Intestinal biopsies from five coeliac patients (selected randomly) and four non-coeliac disease controls who underwent upper endoscopy for intestinal bleeding were challenged with gliadin (0.5 mg/mL) and budesonide (10-30 μg/mL) for 3 and 24 h. Biopsies were tested by immunohistochemistry and immunofluorescence for known markers of inflammation. Treatment of patients with 6 mg budesonide daily for 4 weeks resulted in increased bodyweight, a decreased number of evacuations and decreased stool weight compared with patients on a gluten-free diet alone for 4 weeks. Well-being scores were higher in patients treated with both a gluten-free diet and budesonide compared with those receiving a gluten-free diet alone. In vitro studies showed that budesonide reduced epithelial tyrosine phosphorylation and expression of histocompatibility leucocyte antigen complex DR (HLA-DR) elicited by gliadin-derived peptides. In addition, the expression of cyclo-oxygenase (COX)-2 and intercellular adhesion molecule (ICAM)-1 in the lamina propria was reduced in patients treated with both gliadin and budesonide compared with patients treated with gliadin alone. Budesonide alone decreased HLA-DR in crypt enterocytes, as well as ICAM-1 and COX-2 expression in the lamina propria of biopsy specimen of coeliac patients. Budesonide had no effect in control samples. In conclusion, the results of the present study indicate that budesonide shows efficacy in the treatment of symptoms in adult coeliac patients with overt malabsorption. The mechanism underlying the effects of budesonide in reducing symptoms was elucidated by in vitro studies involving a gliadin challenge.

Original languageEnglish
Pages (from-to)1170-1176
Number of pages7
JournalClinical and Experimental Pharmacology and Physiology
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2009

Keywords

  • Budesonide
  • Coeliac disease
  • Gastrointestinal symptoms
  • Gluten-free diet
  • Malabsorption

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

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