Interleukin-6-deficient mice resist development of experimental autoimmune cardiomyopathy induced by immunization of β1-adrenergic receptor.

• 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. MATERIALS AND 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, 13weeks and observed until 25weeks. 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, Adrb1and GRK2. CONCLUSION: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

β1-Adrenergic receptor; IL-6; Cardiac function; Immunization; Cardiomyopathy

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