PMID- 11156888
OWN - NLM
STAT- MEDLINE
DCOM- 20010524
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 103
IP  - 5
DP  - 2001 Feb 6
TI  - Tumor necrosis factor-alpha (TNF-alpha) plays a protective role in acute 
      viralmyocarditis in mice: A study using mice lacking TNF-alpha.
PG  - 743-9
AB  - BACKGROUND: It has been reported that tumor necrosis factor-alpha (TNF-alpha) is 
      expressed in the heart with viral myocarditis and that its expression aggravates 
      the condition. The pathophysiological effects of TNF-alpha on viral myocarditis, 
      however, have not been fully elucidated. METHODS AND RESULTS: To investigate the 
      role of TNF-alpha in the progression of viral myocarditis, we used TNF-alpha 
      gene-deficient mice (TNF-alpha(-/-)) and induced acute myocarditis by infection 
      with encephalomyocarditis virus (EMCV). The survival rate of TNF-alpha(-/-) mice 
      after EMCV infection was significantly lower than that of TNF-alpha(+/+) mice (0% 
      versus 67% on day 14). Injection of recombinant human TNF-alpha (0.2 to 4.0 
      microg/mouse IV) improved the survival of TNF-alpha(-/-) mice in a dose-dependent 
      manner, indicating that TNF-alpha 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-alpha(-/-) than in TNF-alpha(+/+) 
      mice. Histopathological examination showed that the inflammatory changes of the 
      myocardium were less marked in TNF-alpha(-/-) than in TNF-alpha(+/+) 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-alpha(-/-) mice compared with TNF-alpha(+/+) 
      mice. CONCLUSIONS: These observations suggested that TNF-alpha 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-alpha plays a protective role in the acute stage of 
      viral myocarditis.
FAU - Wada, H
AU  - Wada H
AD  - Department of Laboratory Medicine, Gifu University School of Medicine, Gifu, 
      Japan. wadah@cc.gifu-u.ac.jp
FAU - Saito, K
AU  - Saito K
FAU - Kanda, T
AU  - Kanda T
FAU - Kobayashi, I
AU  - Kobayashi I
FAU - Fujii, H
AU  - Fujii H
FAU - Fujigaki, S
AU  - Fujigaki S
FAU - Maekawa, N
AU  - Maekawa N
FAU - Takatsu, H
AU  - Takatsu H
FAU - Fujiwara, H
AU  - Fujiwara H
FAU - Sekikawa, K
AU  - Sekikawa K
FAU - Seishima, M
AU  - Seishima M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
CIN - Circulation. 2001 Feb 6;103(5):626-9. PMID: 11156870
MH  - Acute Disease
MH  - Alanine Transaminase/metabolism
MH  - Analysis of Variance
MH  - Animals
MH  - Blood Urea Nitrogen
MH  - Creatine Kinase/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Immunohistochemistry
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocarditis/enzymology/metabolism/*prevention & control/virology
MH  - RNA, Messenger/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/metabolism/*therapeutic use
MH  - Viral Load
EDAT- 2001/02/07 11:00
MHDA- 2001/05/26 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/05/26 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1161/01.cir.103.5.743 [doi]
PST - ppublish
SO  - Circulation. 2001 Feb 6;103(5):743-9. doi: 10.1161/01.cir.103.5.743.