The effects of atorvastatin on gluten-induced intestinal T cell responses in coeliac disease

Clin Exp Immunol. 2005 Nov;142(2):333-40. doi: 10.1111/j.1365-2249.2005.02915.x.

Abstract

Various experimental models suggest that the cholesterol-lowering drugs statins may also modulate immune responses. Cellular level studies on human disorders are needed, however, to provide a rational basis for clinical testing of statins as immune therapy. Coeliac disease, a chronic small intestinal inflammation driven by HLA-DQ2 restricted mucosal T cells that are specific for ingested wheat gluten peptides, is in many ways ideal for this purpose. In addition, there is a need for alternative treatment to the gluten-free diet in this disorder. Here we have assessed the effects of atorvastatin on gluten-reactive T cells, dendritic cells and the coeliac mucosa by in vitro culture of biopsies. Atorvastatin inhibited gluten-induced proliferation and specific cytokine production of human intestinal gluten-reactive T cell clones and lines. Dendritic cells exposed to atorvastatin displayed a reduced expression of the costimulatory molecule CD83 upon maturation with lipopolysaccharide. Incubation of intestinal biopsy specimens with atorvastatin in vitro, however, did not influence gluten-induced cytokine release. In conclusion, atorvastatin has specific effects on isolated gluten-reactive T cells and dendritic cells, but does not shut down the gluten-induced production of proinflammatory cytokines in intestinal biopsies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticholesteremic Agents / pharmacology*
  • Antigens, CD / metabolism
  • Apoptosis / drug effects
  • Atorvastatin
  • Celiac Disease / immunology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dose-Response Relationship, Immunologic
  • Glutens / immunology*
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Immunity, Cellular / drug effects
  • Immunity, Mucosal / drug effects
  • Immunoglobulins / metabolism
  • Intestinal Mucosa / immunology
  • Lymphocyte Activation / drug effects
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Organ Culture Techniques
  • Pyrroles / pharmacology*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Up-Regulation / drug effects

Substances

  • Anticholesteremic Agents
  • Antigens, CD
  • CD83 antigen
  • Cytokines
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunoglobulins
  • Membrane Glycoproteins
  • Pyrroles
  • Glutens
  • Atorvastatin