Cytokine Storm – Treatment with Etanercept – Could it Stop Influenza Death?

Mild cytokine reactions give you a flu like situation where achy all over and malaise. Cytokine storm occurs with certain viral infections and can kill. Etanercept (Enbrel) can block that effect some in the mouse model infected with H1N1.

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.
http://ccforum.com/content/pdf/cc13171.pdf

  • a lethal form of H1N1
  • Given either “2.5 mg/kg of etanercept (dissolved in 0.9% (wt/vol) NaCl) twice daily” intranasally
  • None of Control survived but 30% etanercept did.
  • “etanercept significantly reduced inflammatory cell infiltration (for example, macrophages and neutrophils), inflammatory like receptors 7). “
  • “Etanercept also downregulated and inhibited the cascade proteins of the NF-κB signaling pathway (for example, MyD88, TRIF, NF-κB, and p65), as well as enhanced host control of virus replication.”

Tumor Necrosis Factor plays a complex role in viral infections. A recent article on novel treatments for viral infection:
Novel Approaches and Challenges to Treatment of Central Nervous System Viral Infections
Avindra Nath, Kenneth L. Tyler
ANN NEUROL 2013;74:412–422

http://onlinelibrary.wiley.com/doi/10.1002/ana.23988/pdf

“the role of TNFa may be complex, with some aspects facilitating neuroinvasion and others facilitating antiviral roles including accumulation of CD81 T cells and macrophages”

They also found doxycycline has anti-cytokine effects:

“In a clinical study on infection by the flavivirus dengue, doxycycline treatment (200mg load then 100mg every 12 hours 3 10 days) was shown to reduce serum levels of a variety of proinflammatory cytokines (IL6, IL1b, TNF) whose expression has been linked to increasingly severe disease at days 3 and 7 post-treatment compared to controls.86”
86. Castro JE, Vado-Solis I, Perez-Osorio C, Fredeking TM.
Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever.
Clin Dev Immunol 2011;2011:370872.

Comment – in serious influenza, using doxycycline 200 initially and then 100 bid with food and Enbrel injections ( ? part BID) could potentially be helpful.

 

 

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One Response to Cytokine Storm – Treatment with Etanercept – Could it Stop Influenza Death?

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