The novel adipocytokine visfatin is activated in inflammatory bowel disease

A. R. Moschen; B. Enrich; A. Kaser; H. Santner; H. Niederegger; H. Tilg

doi:10.1055/s-2006-955550

Zeitschrift für Gastroenterologie, Table of Contents

The novel adipocytokine visfatin is activated in inflammatory bowel disease

AR Moschen ¹, B Enrich ¹, A Kaser ¹, H Santner ¹, H Niederegger ², H Tilg ¹

¹Department of Medicine, Clinical Division of Gastroenterology and Hepatology
²Innsbruck Biocentre, Division of Experimental Pathophysiology and Immunology, Innsbruck Medical University, Innsbruck, Austria

Abstract

Background: Adipocytokines are a family of proteins that are mainly derived from adipose tissue. Adipocytokines like leptin and adiponectin have been shown to be involved in the pathogenesis of intestinal inflammation. Recently, a novel adipocytokine – visfatin – has been identified. Besides visfatin's extraordinary property as insulin-mimicking cytokine, several reports and our current experimental data suggest that visfatin acts as a pro-inflammatory cytokine. In this work we determined the activation state of human visfatin in patients with inflammatory bowel disease.

Methods: Serum samples of 56 patients with inflammatory bowel disease (IBD) (Crohn's Disease, n=30; ulcerative colitis, n=26) and healthy controls (n=37) were assayed for visfatin by a specific enzyme immuno assay. Total RNA was extracted from involved, non-involved, and control colonic biopsy specimens and relative visfatin expression determined by quantitative real-time PCR. Cryo-sections were double-stained and cellular sources determined by confocal microscopy.

Results: Circulating levels of visfatin were significantly elevated in IBD patients compared to healthy controls. Disease activity – as determined by Crohn's disease activity index (CDAI) and Rachmilewitz clinical activity score (CAI) – was associated with higher visfatin levels in patients with ulcerative colitis (UC) but not in patients with Crohn's disease (CD) who showed elevated visfatin levels irrespective of disease activity. Colonic visfatin mRNA expression was significantly up-regulated in inflammatory colonic biopsy specimens of both CD and UC patients compared to control subjects. As determined by confocal microscopy, the strongest visfatin expression was detected in antigen-presenting cells (APCs) – macrophages (CD163⁺) and dendritic cells (DC-Sign⁺) – of the submucosa. Moreover, visfatin was found in colonic epithelial cells (CK18⁺), mesenteric adipocytes and colonic smooth muscle cells (SMA⁺).

Conclusions: In the present study we demonstrate that the recently characterized adipocytokine visfatin is upregulated in inflammatory bowel disease. The particularly strong expression in APCs might be a hint that visfatin could bear a special impact in cells of the monocyte/macrophage system what will be subject of further investigations.