The effects of atorvastatin on gluten-induced intestinal T cell responses in coeliac disease.
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.
Ráki
M
M
Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, Norway. melinda.raki@medisin.uio.no
Molberg
O
O
Tollefsen
S
S
Lundin
K E A
KE
Sollid
L M
LM
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D002446:Celiac Disease / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005983:Glutens / Q000276:immunology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D018928:Immunity, Mucosal / Q000187:drug effects; D007136:Immunoglobulins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009924:Organ Culture Techniques; D011758:Pyrroles / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects; D000097802:CD83 Antigen
D000924:Anticholesteremic Agents; D015703:Antigens, CD; D000069059:Atorvastatin; D016207:Cytokines; D005983:Glutens; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011758:Pyrroles; D000097802:CD83 Antigen