Overexpression of interleukin-6 aggravates viral myocarditis: impaired increase in tumor necrosis factor-alpha.
The process of inflammation and immune response is regulated by proinflammatory cytokines. Interleukin-6 (IL-6), one of the proinflammatory cytokines, plays a potentially critical role in viral-induced myocarditis. Our previous work demonstrates that exogenous IL-6 administration, given at the time of encephalomyocarditis virus (EMCV) inoculation in C3H/HeJ mice, has a protective effect on myocardium and improves survival rates. In the present study, we examined whether overexpression of IL-6 modified viral myocarditis. On day 3 and 10 after inoculation with EMCV, the ratio of heart weight to body weight and myocardial injury were significantly increased in IL-6 transgenic mice (IL-6TG). On day 3, a reduction of viral clearance was shown by the presence of elevated viral titers and viral replication in the heart of IL-6TG. The concentrations of serum tumor necrosis factor- alpha (TNF alpha) were dramatically increased in wild-type mice on day 1, in contrast, this change was not observed in IL-6TG. Treatment with recombinant human TNF (2 microg) significantly improved viral clearance in the IL-6TG hearts. Thus, overexpression of IL-6 promotes myocardial injury by interrupting both the cytokine network and viral clearance. These experiments suggest the possibility that IL-6 is one of the factors that accelerates tissue damage, including myocardial injury, in the viral myocarditis.
Tanaka
T
T
Second Department of Internal Medicine, Gunma University School of Medicine, 3-39-15, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
Kanda
T
T
McManus
B M
BM
Kanai
H
H
Akiyama
H
H
Sekiguchi
K
K
Yokoyama
T
T
Kurabayashi
M
M
D000818:Animals; D001835:Body Weight; D018188:Cardiovirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000821:virology; D006801:Humans; D017403:In Situ Hybridization; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014779:Virus Replication
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha