title: Effects of simvastatin on circulating autoantibodies to oxidized LDL antigens: relation with immune stimulation markers.
abstract: Statins exert a number of anti-inflammatory and immunomodulatory effects in vitro. However, the immunomodulatory effects in vivo are less clarified. In the present study, we investigated whether simvastatin treatment changed the levels of autoantibodies against specific oxidized LDL (oxLDL) antigens as well as their association with leukocyte activation markers. Eighty volunteers with mild-to-moderate hypercholesterolemia were randomized to either simvastatin 40 mg or placebo for 6 weeks. Autoantibodies against apo B peptide antigens, C-reactive protein (CRP) and interleukin (IL)-6 in plasma were determined by ELISA. Subsets of circulating B and T cells were studied by flow cytometry. Simvastatin significantly reduced CRP by 26%, whereas IL-6 remained unchanged. Levels of IgG against the apo B peptide P-240 (amino acids 3586-3605) increased by 16% (p = 0.03) in the simvastatin group whereas autoantibody levels to other apo B peptides did not change. At baseline and after 6 weeks, the P-240 IgG levels were significantly correlated with the number of CD57+CD28 - CD8+T cells but not to other lymphocyte subsets or inflammatory markers. The P-240 IgG levels after 6 weeks simvastatin therapy was strongly correlated to the relative increase in CD57+CD28 - CD8+T cells (p = 0.003). Simvastatin treatment induced an increase in autoantibodies against an oxLDL antigen. The effect was related to an expansion of a CD8+T cell subset and may involve an immunostimulation by simvastatin.
authors.affiliation: Department of Cardiology, Malmo University Hospital, Sweden. isabel.goncalves@med.lu.se
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
authors.forename: Pierre
authors.initials: P
authors.lastname: Cherfan
authors.forename: Ingrid
authors.initials: I
authors.lastname: Söderberg
authors.forename: Gunilla
authors.initials: G
authors.lastname: Nordin Fredrikson
authors.forename: Lena
authors.initials: L
authors.lastname: Jonasson
mesh_terms: D000917:Antibody Formation / Q000187:drug effects*; D053299:Apolipoprotein B-100 / Q000276:immunology; D001053:Apolipoproteins / Q000097:blood; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002452:Cell Count; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000097:blood; D008077:Lipoproteins, LDL / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D019821:Simvastatin / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D053299:Apolipoprotein B-100; D001053:Apolipoproteins; D001323:Autoantibodies; D008078:Cholesterol, LDL; C508600:IL6 protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; C524806:apolipoprotein B-100 (661-680), human; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein; D002784:Cholesterol; D019821:Simvastatin