PMID- 8313574
OWN - NLM
STAT- MEDLINE
DCOM- 19940318
LR  - 20190623
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 89
IP  - 2
DP  - 1994 Feb
TI  - Therapeutic effect of anti-tumor necrosis factor-alpha antibody on the murine 
      model of viral myocarditis induced by encephalomyocarditis virus.
PG  - 846-51
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been reported to have an 
      antiviral effect in vitro; however, its in vivo effect remains to be clarified. 
      METHODS AND RESULTS: To investigate the role of TNF-alpha in viral myocarditis 
      using a murine model induced by encephalomyocarditis virus (EMCV), we evaluated 
      (1) plasma TNF-alpha levels by enzyme-linked immunosorbent assay (ELISA), (2) the 
      effect of recombinant human TNF-alpha for its possible antiviral effect in vivo, 
      and (3) the effect of anti-murine TNF-alpha monoclonal antibody (mAb) in vivo. 
      Four-week-old DBA/2 mice were inoculated intraperitoneally with EMCV (day 0). 
      Mice were injected intravenously daily with 1 microgram of TNF-alpha or 2 x 10(3) 
      units of anti-TNF-alpha mAb starting on day -1, day 0, or day 1 until day 2 
      (TNF-alpha study) or day 4 (anti-TNF-alpha mAb study). A portion of the mice were 
      killed on day 5 (protocol 1); their hearts were removed, and plaque assays were 
      performed to demonstrate the myocardial virus content. The remaining mice were 
      killed on day 14 (protocol 2); myocardial lesions were examined 
      histopathologically in terms of severity, and their survival rates were 
      determined. Plasma TNF-alpha concentration was elevated in the blood of infected 
      mice compared with uninfected mice 3, 5, and 7 days after virus inoculation. The 
      myocardial virus content was higher in the TNF-alpha-treated group than in the 
      control group. Histopathological analysis revealed that myocardial necrosis and 
      cellular infiltration were more prominent in the TNF-alpha group than in the 
      control group. The anti-TNF-alpha mAb improved survival and myocardial lesions 
      when its treatment was started 1 day before virus inoculation. However, it showed 
      no therapeutic effect when administered simultaneously with the inoculation or on 
      day 1. CONCLUSIONS: TNF-alpha may play an important role in the very early stage 
      of the immune response, and anti-TNF-alpha mAb may prevent the early pathway of 
      acute viral myocarditis.
FAU - Yamada, T
AU  - Yamada T
AD  - Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
FAU - Matsumori, A
AU  - Matsumori A
FAU - Sasayama, S
AU  - Sasayama S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*therapeutic use
MH  - *Cardiovirus Infections
MH  - *Encephalomyocarditis virus
MH  - Mice
MH  - Mice, Inbred DBA
MH  - Myocarditis/*microbiology/mortality/*therapy
MH  - Myocardium/pathology
MH  - Survival Analysis
MH  - Tumor Necrosis Factor-alpha/analysis/*immunology/pharmacology
EDAT- 1994/02/01 00:00
MHDA- 1994/02/01 00:01
CRDT- 1994/02/01 00:00
PHST- 1994/02/01 00:00 [pubmed]
PHST- 1994/02/01 00:01 [medline]
PHST- 1994/02/01 00:00 [entrez]
AID - 10.1161/01.cir.89.2.846 [doi]
PST - ppublish
SO  - Circulation. 1994 Feb;89(2):846-51. doi: 10.1161/01.cir.89.2.846.