What question did this study set out to answer?

To evaluate the pathophysiological function of tumor necrosis factor-alpha (TNF-alpha) in the host response and progression of acute viral myocarditis.

February 6, 2001Circulation

Tumor Necrosis Factor-α (TNF-α) Plays a Protective Role in Acute Viral Myocarditis in Mice

View Full Paper

Ask AI

Bookmark

Why the study?

Does recombinant human TNF-alpha improve survival in TNF-alpha deficient mice with acute viral myocarditis?

Population

TNF-alpha gene-deficient mice (TNF-alpha) and wild-type mice (TNF-alpha) with acute myocarditis induced by…

Comparison

Recombinant human TNF-alpha vs Untreated TNF-alpha mice and wild-type TNF-alpha…

Design

Preclinical

Follow-up

14 days

Authors

HWHisayasu WadaKinan Hospital KSKuniaki SaitoNational Institute of Genetics TKTsugiyasu KandaKanazawa Medical University

Discussion

Member takes

Implication

TNF-alpha may protect against fatal murine viral myocarditis; challenges prior reports of harm and leaves open human translation.

Key Points

To evaluate the pathophysiological function of tumor necrosis factor-alpha (TNF-alpha) in the host response and progression of acute viral myocarditis.
Infected TNF-alpha gene-deficient (TNF-alpha-/-) and wild-type (TNF-alpha+/+) mice with encephalomyocarditis virus (EMCV) to induce acute myocarditis.
Administered recombinant human TNF-alpha intravenously (0.2 to 4.0 µg/mouse) to test dose-dependent survival rescue.
Assessed myocardial viral titers, viral genomic RNA, histopathology, and ICAM-1 and VCAM-1 adhesion molecule expression via immunohistochemistry.
Survival rate at day 14 after EMCV infection was 0% in TNF-alpha(-/-) mice compared to 67% in TNF-alpha(+/+) mice, and treatment with recombinant TNF-alpha restored survival in a dose-dependent manner.
TNF-alpha(-/-) mice showed significantly higher myocardial viral titers and viral genomic RNA levels despite exhibiting less pronounced inflammatory changes on histopathological exam.
Myocardial immunoreactivity of adhesion molecules ICAM-1 and VCAM-1 was decreased in TNF-alpha(-/-) mice compared to TNF-alpha(+/+) controls.

Structured PICO

Does recombinant human TNF-alpha improve survival in TNF-alpha deficient mice with acute viral myocarditis?

Population

TNF-alpha gene-deficient mice (TNF-alpha(-/-)) and wild-type mice (TNF-alpha(+/+)) with acute myocarditis induced by encephalomyocarditis virus (EMCV) infection

Intervention

Recombinant human TNF-alpha (0.2 to 4.0 microg/mouse IV)

Comparator

Untreated TNF-alpha(-/-) mice and wild-type TNF-alpha(+/+) mice

Outcome

Survival rate on day 14hard clinical

Contrary to previous reports suggesting TNF-alpha aggravates viral myocarditis, this study demonstrates it is essential for protection and survival in the acute stage by facilitating leukocyte recruitment.

Cite This Study

Wada et al. (2001) studied this question.

synapsesocial.com/papers/6a76328044a4e9d4ca008b32 https://doi.org/10.1161/01.cir.103.5.743

Topics

Myocarditis

View Full Paper

Ask AI

Bookmark

Tumor Necrosis Factor-α (TNF-α) Plays a Protective Role in Acute Viral Myocarditis in Mice

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Tumor Necrosis Factor-α (TNF-α) Plays a Protective Role in Acute Viral Myocarditis in Mice

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider