Tumor necrosis factor-α (TNF-α) plays a protective role in acute viral myocarditis in mice: A study using mice lacking TNF-α

Hisayasu Wada, Kuniaki Saito, Tsugiyasu Kanda, Isao Kobayashi, Hidehiko Fujii, Suwako Fujigaki, Naoya Maekawa, Hisato Takatsu, Hisayoshi Fujiwara, Kenji Sekikawa, Mitsuru Seishima

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94 Citations (Scopus)

Abstract

Background - It has been reported that tumor necrosis factor-α (TNF-α) is expressed in the heart with viral myocarditis and that its expression aggravates the condition. The pathophysiological effects of TNF-α on viral myocarditis, however, have not been fully elucidated. Methods and Results - To investigate the role of TNF-α in the progression of viral myocarditis, we used TNF-α gene-deficient mice (TNF-α-/-) and induced acute myocarditis by infection with encephalomyocarditis virus (EMCV). The survival rate of TNF-α-/- mice after EMCV infection was significantly lower than that of TNF-α+/+ mice (0% versus 67% on day 14). Injection of recombinant human TNF-α (0.2 to 4.0 μg/mouse IV) improved the survival of TNF-α-/- mice in a dose-dependent manner, indicating that TNF-α is essential for protection against viral myocarditis. The levels of viral titer and viral genomic RNA of EMCV in the myocardium were significantly higher in TNF-α-/- than in TNF-α+/+ mice. Histopathological examination showed that the inflammatory changes of the myocardium were less marked in TNF-α-/- than in TNF-α+/+ mice. Immunohistochemical analysis revealed that the levels of immunoreactivity of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the myocardium were decreased in TNF-α-/- mice compared with TNF-α+/+ mice. Conclusions - These observations suggested that TNF-α is necessary for adhesion molecule expression and to recruit leukocytes to inflammatory sites, and thus, the lack of this cytokine resulted in failure of elimination of infectious agents. We concluded that TNF-α plays a protective role in the acute stage of viral myocarditis.

Original languageEnglish
Pages (from-to)743-749
Number of pages7
JournalCirculation
Volume103
Issue number5
DOIs
Publication statusPublished - 06-02-2001

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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