tetano
Editor, Senior Moderator
Crit Care. 2013 Dec 27;17(6):R301. [Epub ahead of print]
Inhibition of the inflammatory cytokine tumor necrosis factor-alpha with etanercept provides protection against lethal H1N1 influenza infection in mice.
Shi X, Zhou W, Huang H, Zhu H, Zhou P, Zhu H, Ju D.
Abstract
INTRODUCTION:
Factors implicated in influenza mediated morbidity and mortality include robust cytokine production (cytokine storm), excessive inflammatory infiltrates, and virus induced tissue destruction. Tumor necrosis factor-alpha (TNF-alpha) is an important pro-inflammatory cytokine present during influenza infection, but it is unclear whether direct inhibition of TNF-alpha can elicit protection against influenza infection.
METHODS:
In this study, the commercially available TNF-alpha inhibitor etanercept was used to inhibit TNF-alpha induced by lethal A/FM/1/47 (H1N1) influenza virus infection of mice. The effects of TNF-alpha inhibition on mouse survival, pathological changes, immune cell infiltration, inflammatory cytokine secretion, toll-like receptor expression, and activation of the NF-kappaB (nuclear factor kappa B) signaling pathway were evaluated.
RESULTS:
The intranasal delivery of etanercept provided significant protection against mortality (30% of mice survived up to 14 days post infection) in mice treated with etanercept. In contrast, there were no survivors beyond six days in mice treated with saline following lethal challenge with H1N1 influenza virus. It was observed that etanercept significantly reduced inflammatory cell infiltration (e.g. macrophages and neutrophils), inflammatory cytokine secretion (e.g., interleukin 6, TNF-alpha, and interferon gamma), and expression of toll-like receptors (TLR-3, TLR-4, and TLR-7). Etanercept also down-regulated and inhibited the cascade proteins of the NF-kappaB signaling pathway (e.g., MyD88, TRIF, NF-kappaB p65), as well as enhance host control of virus replication.
CONCLUSIONS:
These findings indicated that etanercept, by blocking TNF-alpha, can significantly down-regulate excessive inflammatory immune responses and provide protection against lethal influenza infection making it a novel strategy for controlling severe influenza-induced viral pneumonia.
PMID:
24373231
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24373231
Inhibition of the inflammatory cytokine tumor necrosis factor-alpha with etanercept provides protection against lethal H1N1 influenza infection in mice.
Shi X, Zhou W, Huang H, Zhu H, Zhou P, Zhu H, Ju D.
Abstract
INTRODUCTION:
Factors implicated in influenza mediated morbidity and mortality include robust cytokine production (cytokine storm), excessive inflammatory infiltrates, and virus induced tissue destruction. Tumor necrosis factor-alpha (TNF-alpha) is an important pro-inflammatory cytokine present during influenza infection, but it is unclear whether direct inhibition of TNF-alpha can elicit protection against influenza infection.
METHODS:
In this study, the commercially available TNF-alpha inhibitor etanercept was used to inhibit TNF-alpha induced by lethal A/FM/1/47 (H1N1) influenza virus infection of mice. The effects of TNF-alpha inhibition on mouse survival, pathological changes, immune cell infiltration, inflammatory cytokine secretion, toll-like receptor expression, and activation of the NF-kappaB (nuclear factor kappa B) signaling pathway were evaluated.
RESULTS:
The intranasal delivery of etanercept provided significant protection against mortality (30% of mice survived up to 14 days post infection) in mice treated with etanercept. In contrast, there were no survivors beyond six days in mice treated with saline following lethal challenge with H1N1 influenza virus. It was observed that etanercept significantly reduced inflammatory cell infiltration (e.g. macrophages and neutrophils), inflammatory cytokine secretion (e.g., interleukin 6, TNF-alpha, and interferon gamma), and expression of toll-like receptors (TLR-3, TLR-4, and TLR-7). Etanercept also down-regulated and inhibited the cascade proteins of the NF-kappaB signaling pathway (e.g., MyD88, TRIF, NF-kappaB p65), as well as enhance host control of virus replication.
CONCLUSIONS:
These findings indicated that etanercept, by blocking TNF-alpha, can significantly down-regulate excessive inflammatory immune responses and provide protection against lethal influenza infection making it a novel strategy for controlling severe influenza-induced viral pneumonia.
PMID:
24373231
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24373231