title: Expression of cytokine genes and presence of enteroviral genomic RNA in endomyocardial biopsy tissues of myocarditis and dilated cardiomyopathy.
abstract: Viral infection, especially by enteroviruses, has been considered to be the most common cause of myocarditis, which may progress to dilated cardiomyopathy (DCM). Although the mechanism of progression remains uncertain, a cytokine-associated injury of myocytes has been proposed. Using reverse transcriptase polymerase chain reaction (RT-PCR), we examined the expression of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha) and the presence of enteroviral genomic RNA in endomyocardial biopsy tissues obtained from patients with myocarditis and DCM. We examined endomyocardial biopsy tissues obtained from 6 patients with myocarditis, 21 with DCM and 15 with non-infectious cardiac diseases as controls. In patients with myocarditis, endomyocardial biopsy was performed twice at an interval of 1 month to 8 years after the onset of myocarditis. We used RT-PCR to detect IL-1 beta, IL-6, IL-8 and TNF-alpha genes expression and nested RT-PCR (nRT-PCR) to detect enteroviral genomic RNA. IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in 100% (6/6) and enteroviral genomic RNA in 67% (4/6) of myocarditis patients at the first biopsy. At the second biopsy, IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in none, 50% (3/6), 67% (4/6) and 67% (4/6), respectively, and enteroviral genomic RNA in 67% (4/6). Four patients with myocarditis, in whom IL-8 and TNF-alpha genes and enteroviral genomic RNA were detected, progressed to DCM at the second biopsy. IL-1 beta, IL-6, IL-8 and TNF-alpha genes were expressed in none, 24% (5/21), 38% (8/21), 57% (12/21) of DCM patients, respectively. Enteroviral genomic RNA was detected in 43% (9/21) of DCM. Neither cytokine expression nor enteroviral genomic RNA were detected in the controls. the high incidence of cytokines, especially IL-6, IL-8 and TNF-alpha, expression in myocarditis and DCM, which might be induced by enteroviral infection, suggests that cytokines play an important role in myocytic damage leading to DCM.
authors.affiliation: Second Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.forename: G
authors.initials: G
authors.lastname: Tamura
authors.forename: I
authors.initials: I
authors.lastname: Segawa
authors.forename: A
authors.initials: A
authors.lastname: Tashiro
authors.forename: K
authors.initials: K
authors.lastname: Hiramori
authors.forename: R
authors.initials: R
authors.lastname: Satodate
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology* / Q000821:virology; D016207:Cytokines / Q000235:genetics*; D004699:Endocardium / Q000737:chemistry / Q000473:pathology* / Q000821:virology*; D004769:Enterovirus Infections / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009205:Myocarditis / Q000235:genetics / Q000473:pathology* / Q000821:virology; D012367:RNA, Viral / Q000032:analysis*
chemical_list: D016207:Cytokines; D012367:RNA, Viral