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

• Published in: Clinical and experimental immunology Vol. 142; no. 2; pp. 333 - 340
• Main Authors: Ráki, M., Molberg, Ø., Tollefsen, S., Lundin, K. E. A., Sollid, L. M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2005; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Adult; Aged; Anticholesteremic Agents - pharmacology; Antigens, CD - metabolism; Apoptosis - drug effects; Atorvastatin; Biological and medical sciences; biopsy; CD83 Antigen; Celiac Disease - immunology; Cells, Cultured; Clinical Studies; coeliac disease; Cytokines - metabolism; dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dose-Response Relationship, Immunologic; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glutens - immunology; Heptanoic Acids - pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Immunity, Cellular - drug effects; Immunity, Mucosal - drug effects; Immunoglobulins - metabolism; Immunopathology; Intestinal Mucosa - immunology; Lymphocyte Activation - drug effects; Medical sciences; Membrane Glycoproteins - metabolism; Middle Aged; Organ Culture Techniques; Pyrroles - pharmacology; T cells; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Up-Regulation - drug effects; Immunopathology; Dendritic cell; Immune response; Digestive system; Enzyme; Enzyme inhibitor; Statin derivative; Coeliac disease; T cells; Immunology; dendritic cells; Intestinal malabsorption; Biopsy; Antigen presenting cell; T-Lymphocyte; Atorvastatin; Digestive diseases; Hydroxymethylglutaryl-CoA reductase; Intestinal disease; Oxidoreductases; Gluten
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2005.02915.x

Summary 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.