Cytokine production and antibodies against heat shock protein 60 in cardiomyopathies of different origins.
OBJECTIVE
There is growing evidence that proinflammatory cytokines play an important role in a variety of cardiac pathophysiological conditions. The purpose of this study was to determine the circulating tumour necrosis factor (TNF) and interleukin-6 (IL-6) levels in patients with dilated cardiomyopathy (DCM) (n = 40) or ischaemic heart disease (IHD) (n = 38) in comparison with the corresponding data from patients with hypertrophic cardiomyopathy (HCM) (n = 10) or valvular aorta stenosis (AS) (n = 10) and from healthy blood donors (n = 20).


METHODS
To investigate the possible sources of cytokines, the in vitro cytokine-inducing capacity of the patients' peripheral blood leucocytes was also measured. The TNF and IL-6 expression levels in the myocardium were investigated from biopsy specimens. The study of the immunological background of the cardiomyopathies was supplemented with screening of anti-heat shock protein 60 (Hsp60) antibodies in the sera of the patients.


RESULTS
Elevated levels of circulating TNF (25-150 U/ml) and IL-6 (50-500 pg/ml) were found in 85% of the patients in the DCM and IHD groups, whereas only the IL-6 level was elevated (125-500 pg/ml) in the HCM patients. The in vitro TNF-alpha production was higher than in the normal controls only in the DCM group. The ventricular tissue of the DCM patients expressed TNF-alpha and IL-6. In vitro experiments were performed to examine the production of TNF and IL-6 by cultured rat cardiac myocytes (H9C2) under hypoxic conditions. Even a short hypoxic treatment resulted in cytokine production between 4 and 72 h following reoxygenization. Considerable amounts of anti-Hsp60 antibodies were found in 80% of the IHD patients and in 65% of the DCM patients. The in vitro cytokine production of leucocytes and the frequency of anti-Hsp60 positivity in patients with HCM or AS was not significantly different from those in the normal blood donors.


CONCLUSIONS
These results demonstrate that TNF-alpha and IL-6 are of pathophysiological importance in some but not all types of cardiomyopathies, and the sources of cytokine production may differ. The mechanism of the development of primary DCM is still unknown; the high in vitro production of proinflammatory cytokines in the leucocytes of patients with DCM, the presence of TNF and IL-6 in their cardiac tissue and the high prevalence of anti-Hsp60 antibodies in their sera suggest a strong immunological background in the pathophysiology of the disease.
Mándi
Y
Y
Department of Medical Microbiology, Faculty of Medicine, University of Szeged, Dóm tér 10, POB 427, H-6720 Szeged, Hungary. yvette@comber.szote.u-szeged.hu
Hogye
M
M
Talha
E M
EM
Skolák
E
E
Csanády
M
M
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D001323:Autoantibodies; D018834:Chaperonin 60; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha