title: Interleukin-6-deficient mice resist development of experimental autoimmune cardiomyopathy induced by immunization of β1-adrenergic receptor.
abstract: BACKGROUND
  IL-6 is known to be an important mediator in immune response and is now suggested to be involved in the pathogenesis of autoimmune diseases. However, little is known about the role of IL-6 in β(1)-adrenergic receptor induced autoimmune cardiomyopathy.
  
  
  METHODS
  Twenty IL-6-deficient (IL-6(-/-)) mice and fifty-one wild type C57BL/6J (WT) mice were immunized with a synthetic peptide corresponding to the second extracellular loop of the β(1) (β(1)AR ECII) at 0, 1, 5, 9, 13 weeks and observed until 25 weeks. Another forty-one WT mice and twenty IL-6(-/-) mice were used as controls receiving vehicle in the same manner.
  
  
  RESULTS
  As compared with IL-6(-/-) immunized and control mice, WT immunized mice showed increased end-systolic left ventricular dimension and end-diastolic left ventricular dimension as well as decreased fractional shortening and circumferential fiber shortening in the end of the experiment, which was accompanied by significantly increased antibody level. Moreover, mRNAs encoding for β(1)-adrenergic receptor kinase (GRK2), B-type natriuretic peptide (BNP) and β(1) adrenergic receptor (Adrb1) in heart tissues from WT immunized group were increased. There was a significant positive correlation among end-diastolic left ventricular dimension, autoantibody titer and mRNA expressions of BNP, Adrb1 and GRK2.
  
  
  CONCLUSIONS
  Our results demonstrated that immunization with β1AR ECII was unable to induce an early stage phenotype of cardiomyopathy in IL-6(-/-) mice, being different from wild type in which cardiomyopathy was observed, suggesting that IL-6 plays a key role in the regulation of β(1)AR induced autoimmune cardiomyopathy possibly through its enhanced antibody production.
authors.affiliation: Dept of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Liping.Ma@wlab.gu.se
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ma
authors.forename: Goditha
authors.initials: G
authors.lastname: Premaratne
authors.forename: Entela
authors.initials: E
authors.lastname: Bollano
authors.forename: Catharina
authors.initials: C
authors.lastname: Lindholm
authors.forename: Michael
authors.initials: M
authors.lastname: Fu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D009202:Cardiomyopathies / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D015850:Interleukin-6 / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018342:Receptors, Adrenergic, beta-1 / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D018342:Receptors, Adrenergic, beta-1